Articles Of Manufacture Releasing An Active Ingredient

ABSTRACT

The present invention relates to articles of manufacture having a formulation distributed therein, wherein the formulation comprises an active agent which manifests a desirable property when released from the articles of manufacture. The present invention also relates to methods for manufacturing these articles of manufacture, to vehicles for applying the formulation to these articles of manufacture, and to perception indicators indicating the presence and the amount of formulation comprising an active agent applied to an article of manufacture.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of now-allowed U.S. patentapplication Ser. No. 12/680,836, “Articles of Manufacture Releasing anActive Ingredient” (filed Mar. 30, 2010), which is a National StageEntry of PCT/CA09/001012, “Articles of Manufacture Releasing an ActiveIngredient” (filed Jul. 17, 2009), which claims the benefit of andpriority to U.S. provisional application No. 61/081,911 (filed Jul. 18,2008). Each of the preceding applications is incorporated herein byreference in its entirety for any and all purposes.

FIELD OF TECHNOLOGY

The present invention relates to articles of manufacture having aformulation distributed therein, wherein the formulation comprises anactive ingredient which manifests a desirable property when releasedfrom the articles of manufacture. The present invention also relates tomethods for manufacturing such articles and to vehicles for applying theformulation to the articles. Further, the present invention relates toarticles of manufacture having perception indicators indicating thepresence of a formulation dispersed within the articles.

BACKGROUND

There is a need in the art for articles of manufacture, such as, but notlimited to, articles made of woven and non-woven textiles, having anactive ingredient distributed therein, wherein the articles ofmanufacture exhibit a progressive or immediate release of the activeingredient.

There is also a need for formulations that can incorporate one or moreactive ingredient and permit the progressive release of the activeingredient, and for formulations from which microparticles can beobtained and that can be retained in the interstices or pores of thearticles of manufacture.

Additionally, there is a need for a method and identifiers to determineif an article of manufacture has one or more active ingredientsdispersed therein and/or to monitor the amount of the active ingredientsremaining on or released from the article of manufacture.

SUMMARY OF THE INVENTION

In one aspect, the present invention relates to an article ofmanufacture, comprising: a substrate; microparticles distributed in atleast a portion of the substrate, wherein the microparticles include anactive ingredient dispersed within a carrier material, themicroparticles undergoing progressive erosion in response to a stimulusto cause gradual release of the active ingredient; the microparticleshaving a release index of between about 1 and about 20.

In another aspect, the present invention relates to an article ofmanufacture comprising: a substrate; microparticles distributed in atleast a portion of the substrate, wherein the microparticles include anactive ingredient dispersed within a carrier material, themicroparticles undergoing progressive erosion in response to a stimulusto cause gradual release of the active ingredient; wherein after havingbeen through 20 wash cycles, the article of manufacture still maintainsa positive active ingredient release rate.

In another aspect, the present invention relates to an article ofmanufacture comprising: a substrate; microparticles distributed in atleast a portion of the substrate, wherein the microparticles include anactive ingredient dispersed within a carrier material, themicroparticles undergoing progressive erosion in response to a stimulusto cause gradual release of the active ingredient; wherein the articleof manufacture maintains a constant rate of release of the activeingredient between 20 and 40 wash cycles.

In another aspect, the present invention relates to an article ofmanufacture comprising: a substrate; microparticles distributed in atleast a portion of the substrate, wherein the microparticles include anactive ingredient dispersed within a carrier material, themicroparticles undergoing progressive erosion in response to a stimulusto cause gradual release of the active ingredient; wherein the articleof manufacture maintains a constant rate of release of the activeingredient between 10 and 20 wash cycles.

In another aspect, the present invention relates to an article ofmanufacture comprising: a substrate; microparticles distributed in atleast a portion of the substrate, wherein the microparticles include anactive ingredient dispersed within a carrier material, themicroparticles undergoing progressive erosion in response to a stimulusto cause gradual release of the active ingredient; wherein release ofthe active ingredient is maintained between 15 and 20 wash cycles at arate that is about 2 to about 3 times the rate between 30 and 40 washcycles.

In another aspect, the present invention relates to a method forobtaining microparticles having an active ingredient dispersed therein,comprising: forming a stirred melt of a formulation comprising theactive ingredient; and obtaining microparticles from the formulation,wherein the microparticles obtained have the active ingredient dispersedtherein.

In another aspect, the present invention relates to a method forpreparing an article of manufacture as defined herein, comprising:forming a stirred melt of a preparation comprising the activeingredient; obtaining microparticles from the formulation; wherein themicroparticles obtained have the active ingredient dispersed therein;and applying the microparticles to the article of manufacture.

In a further aspect, the present invention relates to a method fordelivering an active ingredient to a subject, comprising: obtaining aformulation of microparticles having the active ingredient dispersedtherein; wherein the microparticles undergo progressive erosion inresponse to a stimulus causing gradual release of the active ingredient;transferring the formulation of microparticles to a substrate; andplacing the substrate in contact with the subject, wherein contact ofthe substrate with the subject causes the active ingredient to bedelivered to the subject.

In a further aspect, the present invention relates to a method fordelivering a therapeutic agent to a subject, comprising: applyingmicroparticles having the therapeutic agent dispersed therein to anarticle of manufacture; wherein the microparticles undergo progressiveerosion in response to a stimulus causing gradual release of thetherapeutic agent; and wearing of the article of manufacture by thesubject; wherein contact of the article of manufacture with thesubject's body causes release of the therapeutic agent to the subject'sbody.

In a further aspect, the present invention relates to a method fordelivering a cosmetic agent to a subject, comprising: applyingmicroparticles having the cosmetic agent dispersed therein to an articleof manufacture; wherein the microparticles undergo progressive erosionin response to a stimulus causing gradual release of the cosmetic agent;and wearing of the article of manufacture of by the subject; whereincontact of the article of manufacture with the subject's body causesrelease of the cosmetic agent to the subject's body.

In a further aspect, the present invention relates to a microparticlefor delivery of an active ingredient, wherein the microparticle: isobtained from a formulation comprising a carrier material; has theactive ingredient dispersed therein; and undergoes progressive erosionin response to a physical stimulus to cause gradual release of theactive ingredient.

In a further aspect, the present invention relates to a microparticlefor delivery of an active ingredient, wherein the microparticle is madefrom stearic acid and palmitic acid and has an active ingredientdispersed therein, the microparticle undergoing progressive erosion inresponse to a stimulus to cause gradual release of the activeingredient.

In a further aspect, the present invention relates to microparticles fordelivery of an active ingredient, wherein one or more of themicroparticles have a size in the range from about 0.1 μm to about 200μm, the microparticles undergo progressive erosion in response to astimulus to cause gradual release of the active ingredient.

In a further aspect, the present invention relates to microparticles fordelivery of an active ingredient, wherein the microparticles have amelting temperature between about 20° C. and about 60° C., themicroparticles undergoing progressive erosion in response to a stimulusto cause gradual release of the active ingredient.

In a further aspect, the present invention relates to a formulation forobtaining microparticles, comprising a carrier material, a binding agentand a surfactant, wherein the carrier material includes a lipid, a fattyacid-based lipid, a fatty acid or a glyceride or any combinationthereof.

In a further aspect, the present invention relates to an applicationvehicle for transferring microparticles to a substrate, comprising: asupport, microparticles applied to the support; wherein themicroparticles include an active ingredient dispersed therein, themicroparticles undergoing progressive erosion in response to a stimulusto cause gradual release of the active ingredient; wherein when thesupport is placed in contact with the substrate, the microparticles aretransferred from the support to the substrate.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a graph showing the release of microparticles, obtained from aTPGMS or a TPMAGMS formulation, from a polyester substrate (P100t) andfrom a nylon-cotton substrate (N70C30), in accordance with anon-limiting example of implementation of the invention.

FIG. 2 is a graph showing the influence of the ratio of bindingagent:microparticles on the retention of microparticles in the substrateafter one wash cycle. The term “ini” refers to the initial amount offormulation applied to the substrate,

FIGS. 3A to 3C are graphs showing the influence of wash cycles on theretention of microparticles in a P100t substrate. In FIG. 3A, themicroparticles are obtained from a LASA formulation. In FIG. 3B, themicroparticles are obtained from a LASAKAR formulation. In FIG. 3C, themicroparticles are obtained from a TPMAGMS formulation. The term “ini”refers to the initial amount of formulation applied to the substrate.The formulations may be provided with binding agent or may be free ofbinding agent.

FIGS. 4A to 4C are graphs showing a release rate constant analysis formicroparticles obtained from a LASA (FIG. 4A), a LASAKAR (FIG. 4B) and aTPMAGMS (FIG. 4C) formulation.

FIG. 5 is a graph indicating the percent of microparticles transferredfrom a solid support onto either a rigid surfaced substrate or a softsurfaced substrate. Microparticles are obtained from the indicatedformulations which may comprise or a binding agent or may be free ofbinding agent.

FIG. 6 is a graph showing the influence of temperature on the release ofmicroparticles from a support onto the skin when the microparticles areobtained from the indicated formulations.

FIG. 7 is a schematic representation of a non-limiting example of amethod for applying microparticles to a substrate using the technique ofscreen-printing.

FIG. 8 is a schematic representation of a non-limiting example of amethod for applying microparticles to a substrate using the technique ofink-jet printing.

FIGS. 9A and 9B are electron micrograph pictures of a polyestersubstrate impregnated with microparticles obtained from a TPMAGMSformulation after 30 wash cycles (FIG. 9B) and a virgin polyestersubstrate (no microparticles applied) after five wash cycles (FIG. 9A).

FIGS. 10A and 10B are pictures with a visual indication that aformulation has been applied to a substrate. FIG. 10A shows a PPFVsupport assembly onto which a pattern of fiber glass has been applied,without formulation and FIG. 10B shows the trace left by the applicationof a formulation on a polyester substrate using the PPFV supportassembly.

FIG. 11 is a schematic representation of a non-limiting example of amethod for transferring a formulation from a PPFV support assembly as inFIG. 10A onto a textile substrate using pressing rollers.

FIG. 12 is a schematic representation of an apparatus used to determinethe retention of microparticles on a substrate subjected to wash cycles.

FIG. 13 is a schematic representation of an undergarment on whichrepetitive circles of formulation have been applied to its interiorsurface, which surface is in contact with the skin of the wearer.

DETAILED DESCRIPTION

The implementations defined below are not intended to be exhaustive orto limit the scope of the application to the precise forms disclosed inthe following detailed description.

I. Microparticles

Microparticles as defined herein are not limited to any particulargeometric shape and can for example be in the form of globules, bits,droplets, may have a spherical shape, an elliptical shape or may have anirregular or discontinuous shape.

The shape of the microparticle may be irregular so as to create physicalattachment points or locations to assist with retention of themicroparticle into or onto a substrate such as, but not limited to, afabric, a textile, fibers, foams or the like, onto which themicroparticle is applied. The surface of the microparticle or partsthereof may be irregular, discontinuous and/or rough. The surface of amicroparticle or parts thereof may also be regular, continuous and/orsmooth.

Due to the methods used to create microparticles, which may include suchtechniques as homogenization, sonication and planetary centrifugalmixers, the shape of microparticles may vary. While the general shape ofmicroparticles can be controlled such as, but not limited to, throughusing the vibrational nozzle technique, it should be appreciated thatfor convenience microparticles are categorized and grouped by their sizerather than by their shape.

In a specific, but non-limiting, example of implementation, themicroparticles have all three dimensions in the range of about 0.1 μm toabout 200 μm, preferably in the range of about 1 μm to about 50 μm andmost preferably in the range of about 2 μm to about 20 μm. Preferably,all three dimensions of the microparticles permit dispersion of anactive ingredient within the microparticles and allow retention of themicroparticles in the substrate onto which the microparticles areapplied, such as for example, in the interstices, pores or cross linkageopenings in a substrate, or onto the substrate itself (e.g., onto thefibers of a textile) or absorbed into the substrate (e.g., absorbed intothe fibers of a textile).

As used herein, the term “size” refers to the largest dimension of themicroparticle.

In a further specific, but non-limiting example, the microparticles havea size that permits the incorporation of one or more nanoparticleshaving an active ingredient dispersed therein. Nanoparticles generallyinclude small particles with all three dimensions less than 100nanometres. Nanoparticles also include subcategories such asnanopowders, nanoclusters and nanocrystals. Nanocluster generally refersto an amorphous/semicrystalline nanostructure with at least onedimension being between about 1 nm and about 10 nm and a narrow sizedistribution. Nanopowder generally refers to an agglomeration ofnoncrystalline nanostructural subunits with at least one dimension lessthan 100 nm. Nanocrystal generally refers to any nanomaterial with atleast one dimension 100 nm and that is singlecrystalline.

Microparticles may be visualized using techniques such as, but notlimited to, extraction method with tracer techniques (e.g., electronmicroscopy). Other techniques to visualize microparticles will be knownto those of skill in the art. The size of the microparticle isdetermined by techniques well known in the art, such as, but not limitedto, photon correlation spectroscopy, laser diffractometry, scanningelectron microscopy and/or 3CCD (charged-couple device).

Visual indicators may also be added to the microparticles to promotetheir visualization. For example, the microparticles may incorporate alabeled dye into or onto the microparticles. Variants of labeledmicroparticles include additional dyes and/or bioreactive substances.

Microparticles may be electrostatically charged or may beelectrostatically uncharged. In particular, the surface of themicroparticles may have a residual positive charge or a residualnegative charge. Methods to assess surface charges of a microparticlewill be apparent to the skilled workers in the art.

Microparticles may be obtained from a formulation comprising a carriermaterial, wherein the carrier material may be hydrophilic orhydrophobic. As intended by the present specification, the formulationrepresents the milieu from which the microparticles are formed and/orthe environment of the formed microparticles. A formulation may or maynot comprise microparticles dispersed therein.

As used herein, the term “hydrophilic” or “hydrophile” refers to aphysical property of a molecule that can transiently bond with waterthrough hydrogen bonding. A hydrophilic molecule or portion of amolecule is one that is typically charge-polarized and capable ofhydrogen bonding, enabling it to dissolve more readily in water than inoil or other hydrophobic solvents.

The term “hydrophobe” or “hydrophobic” refers to the physical propertyof a molecule that is repelled from a mass of water. Hydrophobicmolecules tend to be non-polar and thus prefer other neutral moleculesand non-polar solvents. Examples of hydrophobic molecules includealkanes, oils, fats, and greasy substances in general.

In a specific, but non-limiting implementation of the present invention,the carrier material includes lipids, fatty acid-based lipids,glycerides, fatty acids, paraffin, waxes, or any combination thereof.

Lipids generally include any fat-soluble (lipophilic),naturally-occurring molecules, such as, but not limited to, fats, oils,waxes, cholesterol, sterols, fat-soluble vitamins (such as vitamins A,D, E and K), monoglycerides, diglycerides, phospholipids, and others.Other types of lipids that may be suitable carrier material will bereadily recognized by skilled workers in the art.

As used herein, the term “fatty acid” or “fatty acid moiety” includesaliphatic monocarboxylic acids, derived from, or contained in esterifiedform in an animal or vegetable fat, oil, wax or the like. Natural fattyacids commonly have a chain of 4 to 28 carbons. The fatty acid moietymay be saturated or unsaturated, linear or branched and may be such as,but not limited to, caproic acid, caprylic acid, capric acid, undecanoicacid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid,palmitic acid, heptadecanoic acid, stearic acid, oleic acid, elaidicacid, linoleic acid, linolenic acid, arachidic acid, and arachidonicacid, or a fatty acid derivative such as an aryl-fatty acid derivative(e.g., phenylacetyl) or a cycloalkyl-fatty acid derivative (e.g.,cyclohexylacetyl or cyclohexylpropionyl), arylacyl moieties include, butare not limited to, benzoyl. A person skilled in the art would readilyrecognize a fatty acid or a fatty acid moiety.

Fatty acid-containing lipid includes lipids which comprise fatty acidmoieties. Glycerides or acylglycerols include esters formed fromglycerol and fatty acids.

In one specific, but non-limiting example, the carrier material isglycerol monostearate, tristearin (tristearic acid), tripalmitin (atriglyceride of palmitic acid), stearic acid, palmitic acid, mysiticacid, lauric acid, parafin, bee's wax or any combination thereof.

Table 1 shows examples of carrier materials that may be used ascomponents of the formulation, the proportion in which these carriermaterials may be used and the expected melting temperature of eachcarrier material;

TABLE 1 Examples of carrier material that may be used in theformulations defined herein Melting temp Carrier material KAR GSM TS TPSA PA MA LA (° C.) Shea butter 100 32 (KAR) Glycerol 100 62 monostearate(GMS) Tristearin (TS) 100 60 Tripalmitin (TP) 100 61 Stearic acid 100 56(SA) Palmitic acid 100 62 (PA) Myristic acid 100 53 (MA) Laurie acid(LA) 100 44 SAPA 65 35 48 TSGMS 39 61 50 TSGMS 21 79 50 TPGMS 41 59 45LASA 25 75 32 MASA 31 69 43 TPSAGMS 20 59 21 46 TSSAGMS 20 58 22 47LAGMS 51 49 39 LAMASA 29 49 22 33 TPMAGMS 19 51 30 41 LASAGMS 21 19 6032 MASAGMS 20 23 57 40 LASA 29 71 33 LATS 32 68 33 LASAKAR 13 26 61 31TPMAGMS 25 62 13 44

The formulations may further comprise a surfactant, a binding agent, anactive ingredient, or any combination thereof.

A surfactant may be used in the instant formulations to disperse thecarrier material into water and to confer a residual charge to themicroparticles. The surfactant may be cationic (based on quaternaryammonium cations), anionic (based on sulfate, sulfonate or carboxylateanions), nonionic or amphoteric. Examples of surfactant are, but are notlimited to, sodium dodecyl sulfate (SDS) and other alkyl sulfate salts,sodium laureth sulfate, also known as sodium lauryl ether sulfate(SLES), alkyl benzene sulfonate, soaps, fatty acid salts, cetyltrimethylammonium bromide (CTAB), cetyl trimethylammonium chloride(CTAC) and other alkyltrimethylammonium salts, cetylpyridinium chloride(CPC), polyethoxylated tallow amine (POEA), benzalkonium chloride (BAC),benzethonium chloride (BZT), zwitterionic (amphoteric), dodecyl betaine,dodecyl dimethylamine oxide, cocamidopropyl betaine, coco amphoglycinate, nonionic alkyl poly(ethylene oxide), copolymers ofpoly(ethylene oxide) and poly(propylene oxide) (commercially calledPoloxamers, Pluronics or Poloxamines), alkyl polyglucosides, including:octyl glucoside, decyl maltoside, fatty alcohols, cetyl alcohol, oleylalcohol, cocamide MEA, cocamide DEA, sorbitol ester or fatty acids, orany combination thereof.

Sucrose esters may also be used as surfactant. Sucrose esters suitablefor use in the present invention have been used for other purposes suchas biologically decomposable emulsifiers in food processing, in thepharmaceutical industry, in cosmetics and in household detergentformulations. Sucrose esters consist largely of the sucrose mono- anddi-esters of the natural fatty acids having 12 to 20 carbon atoms andpreferably 16 to 20 carbon atoms. The sucrose esters that may used inthe present invention include sucrose cocoate, sucrose dilaurate,sucrose distearate, sucrose laurate, sucrose myristate, sucrose oleate,sucrose palmitate, sucrose polylaurate, sucrose polylinoleate, sucrosepolyoleate, sucrose polystearate, sucrose stearate, sucrosetetrastearate, sucrose tribehenate, sucrose tristearate or anycombination thereof.

A binding agent may be used in the instant formulations to conferstability to the formulations. Binding agents that may be useful in thepresent invention include, but are not limited to, polyacrylics (alsoreferred herein as PAC), polyurethanes (also referred herein as PU),polysiloxanes (also referred herein as POL), polyvinylpyrrolidone (alsoreferred herein as PVP), guar gum, resin or acrylic base or anycombination thereof. Other binding agents that are useful elements inthe formulations defined herein will be apparent to a person skilled inthe art.

In a specific, but non-limiting implementation of the present invention,the formulation may comprise any combination of the elements listed inTable 2:

TABLE 2 Examples of elements that may be used in the formulationsdefined herein Abbreviations Name used herein Function Glycerolmonostearate GMS carrier material Tristearin TS carrier materialTripalmitin TP carrier material Stearic acid SA carrier materialPalmitic acid PA carrier material Mysitic acid MA carrier materialLauric acid LA carrier material Paraffin PARA carrier material Bee's waxBEE carrier material Shea butter KAR carrier material/ active ingredientCetyl trimethylammonium CTAC surfactant chloride Sodium laureth sulfateESB surfactant PolyAc M-4445 PAC binding agent PU30 PU binding agentPolon POL binding agent PVP K90 PVP binding agent

In a further specific, but non-limiting implementation, the formulationmay comprise any of the following combination of elements:

-   -   LA+SA; also referred herein as LASA;    -   SA+PA; also referred herein as SAPA;    -   LA+SA+PAC; also referred herein as LASA/PAC;    -   LA+SA+KAR; also referred herein as LASAKAR;    -   LA+SA+KAR+PAC; also referred herein as LASAKAR/PAC;    -   TS+MA+GMS; also referred herein as TPMAGMS;    -   TS+MA+GMS+PAC; also referred herein as TPMAGMS/PAC.

In a further specific but not limiting implementation, the formulationmay comprise a natural butter, such as, shea butter, lemon butter, cocoabutter, grape seed butter, mago butter, sal butter, Illipe butter, kokumbutter, pentadesma butter or the like, or any combination thereof. Thenatural butter may also be used as carrier and/or as an activeingredient in the formulations defined herein.

Microparticles may also be obtained from formulations that comprisenatural butters and the microparticles obtained from such formulationalso comprise natural butters. In such embodiment, the microparticlescomprise about 25% to about 40% of natural butters, more preferablyabout 30 to about 35% of natural butters.

In a further specific, but non-limiting implementation, themicroparticles melt at a temperature between about 20° C. to about 60°C.

In a further specific but non-limiting example, the pH of theformulation may be in the range of from about 4 to about 10; preferablyin the range of from about 6 to about 8.

A person skilled in the art will appreciate that other elements andother proportions may be used in the formulations without departing fromthe desired utility of the formulations defined herein.

II. Methods for the Manufacture of Formulations ComprisingMicroparticles

Generally, in the method of manufacturing a formulation comprising themicroparticles, the first step includes the selection of the elementsfor preparing the formulation. For example, such selection includes; 1)selecting one or more carrier material; 2) selecting one or more activeingredient; 3) selecting one or more surfactant; and 4) selecting one ormore binding agent. The selected carrier materials and selected activeingredient(s) are mixed and melted so as to form a liquid phase that ismixed in an aqueous solution of the surfactant that may be pre-heatedand homogenized to obtain microdoplets. The molten liquid or stirredmelt comprising the carrier materials and the active ingredient may bedispersed into microdroplets using techniques such as, but not limitedto, stirring or sonication. Upon cooling, the microdoplets solidify intomicroparticles. The binding agent is added and mixed to the dispersionto form the formulation containing the microparticles. Any variation inthis general method which results in the formation of formulationscomprising microparticles is also encompassed by the presentapplication.

The amounts and ratios of elements composing the formulation; thetemperature at which the elements are melted; the speed, frequency andduration of the homogenization step; the temperature at which theformulation is cooled; are all factors that may affect the composition,concentration, size and resistance of microparticles.

The elements of the formulation have low toxicity and are preferablycompatible with the active ingredient to be incorporated in theformulation. Preferably, the elements of the formulation should notaffect the desirable properties of the active ingredients.

III. Active Ingredient

In a further specific, but non-limiting aspect of the present invention,the microparticles defined herein comprise one or more active ingredientdispersed therein. The active ingredient includes any substance thatmanifests a desirable property, activity, purpose and/or virtue on, forexample a subject or on an object. As used herein, the term “subject”includes humans and animals.

The choice of active ingredient is determined by the desired effect orthe desired property to be manifested. Active ingredients include, butare not limited to pharmaceutical agents, therapeutic agents, medicinalagents, nutraceutical agents, cosmetic agents, cleansing agents,detoxification agents, aromatic agents, flavorings agents,surface-active compositions, beautifying agent, etc. The activeingredient may be a naturally-occurring or a synthetic molecule.

Pharmaceutical active ingredients include agents having a direct orindirect beneficial effect upon introduction into or administration to ahost. The expression pharmaceutical active ingredient is also meant toindicate prodrug forms thereof. A prodrug form of a pharmaceuticalactive ingredient means a structurally related compound or derivative ofthe pharmaceutical active ingredient which, when introduced into oradministered to a host is converted into the desired pharmaceuticalactive ingredient.

Representative examples of pharmaceutical agents include, but are notlimited to: antidiarrhoeals, antihypertensives, calcium channelblockers, antiarrhyrthmics, antiangina agents, beta-adrenergic blockingagents; cardiotonic glycosides, adrenergic stimulants, vasodilators,antimigraine preparations, anticoagulants and thrombolytic agents,hemostatic agents, analgesics and antipyretics, neurotoxins, hypnoticsand sedatives, antianxiety agents, neuroleptic and antipsychotic drugs,antidepressants, CNS stimulants, anti-alzheimer's agents,anti-Parkinson's agents, anticonvulsants, antiemetics and antinauseants,non-steroidal anti-inflammatory agents, antirheumatoid agents, musclerelaxants, agents used in gout and hyperuricaernia, oestrogens,progesterone and other progestagens, antiandrogens, antioestrogens,androgens and anabolic agents, corticosteroids, pituitary hormones andtheir active derivatives or analogs, hypoglycemic agents, thyroidhormones, other miscellaneous hormone agents, pituitary inhibitors,ovulation inducers, diuretics, antidiuretics, obstetric drugs,prostaglandins, antimicrobials, penicillins, tetracyclines,aminoglycosides, antifungals, quinolones, sulphonamides, sulphones,other miscellaneous antibiotics, antituberculosis drugs, antimalarials,antiviral agents, anthelmintics, cytotoxic agents, weight reducingagents, agents used in hypercalcaemia, antitussives, expectorants,decongestants, bronchospasm relaxants, antihistamines, local or topicalanaesthetics, stratum corneum lipids, ceramides, cholesterol and freefatty acids, neuromuscular blocking agents, smoking cessation agents,insecticides and other pesticides which are suitable for local ortopical application, dermatological agents, allergens fordesensitisation, nutritional agents or keratolytics.

A therapeutic agent include agents that are effective to amelioratesymptoms associated with a disease, a disorder or a condition to lessenthe severity or cure the disease, disorder or condition or to preventthe disease, disorder or condition from occurring. The term treatmentrefers to both therapeutic treatments as well as to prophylactic andpreventative measures.

Representative examples of therapeutical agents include, but are notlimited to: acepromazine, acetaminophen, acetohexamide, acetohydroxamicacid, acetylcholine, acetylcysteine acyclovir, albendazole,alclometasone dipropionate, allopurinol, alprazolam, alprostadil,amcinoide, amantadine, amidinocillin, amikacin amiloride, aminocaproicacid, aminophylline, aminosalicylate, aminosalicylic acid, amitriptylinehydrochloride, ammonium chloride, amobarbital, amodiaquinehydrochloride, amoxapine, amoxicillin, amphetamine sulfate,amphotericin, ampicillin amprolium, acetazolamide acetyldigoxin,acetylsalicylic acid, anileridine, anthralin, antipyrine, antivenin,apomorphine, apraclonidine, ascorbic acid, aspirin, acromycin atropine,amoxycillin anipamil, azaperone azatadine maleate, azathioprine,azithromycin, aztreonam, bacampicillin, bacitracin, baclofen, bariumsalts, beclomethasone diproionate, belladonna extract,bendroflumethiazide, benoxinate hydrochloride, benzethonium chloride,benzocaine, benzonatate benzthiazide, benztropine mesylate, betaine,betamethasone, betaxolol, betanechol chloride, biotin, biperiden,bisacodyl, bismuth, botulism antitoxin, bromocriptine mesylate,bromodiphenhydramine hydrochloride, bumetanide, bupivacaine, busulfanbutabarbital sodium, butalbital, combinations of butalbital, caffeineand aspirin and codeine, beta-carotene, calcifediol, calcium carbonate,calcium citrate, calcium salts, candicidin, captopril, carbachol,carbamazepine, carbenicillin indanyl sodium, carbidopa, carbinoxaminemaleate, carboprost tromethamine, carboxymethyl cellulose, carisoprodol,casanthranol, cascara, castor oil, cefaclor, cefadroxil, cefamandolenafate, cefazolin, cefixime, cefoperazone, cefotaxime, cefprozil,ceftazidime, cefuroxime axetil, cephalexin, cephradine, ceramic powder,chlorambucil, chloramphenicol, chlordiazepoxide, chloroquine phosphate,chlormadinone acetate, chlorothiazide, chlorpheniramine maleate,chloroxylenol, chlorpromazin, chlorpropamide, chlorprothixene,chlorprothixene, chlortetracycline bisulfate, chlortetracyclinehydrochloride, chlorthalidone, chlorzoxazone, cholecalciferol, choleravaccine, chromic chloride, chymotrypsin, cimetidine, cinoxazin,cinoxate, ciprofloxacin, cisplatin, clarithromycin, clavulanatepotassium, clemastine fumarate, clidinium bromide, clindamycinhydrochloride, palmitate and phosphate, clioquinol, clofazimine,clofibrate, clomiphene citrate, clonazepam, cinnarizine, clonidinehydrochloride, clorsulon, clotrimazole, cloxacillin sodium,cyanocobalamin, cocaine, coccidioidin, cod liver oil, codeine,colchicine, colestipol, corticotropin, corisone acetate, cyclacillin,cyclizine hydrochloride, cyclobenzaprine hydrochloride,cyclophosphamide, cycloserine, cyclosporine, cyproheptadinehydrochloride, cysteine hydrochloride, danazol, dapsone, dehydrocholicacid, demeclocycline, desipramine, desoximetasone, desoxycorticosteroneacetate, dexamethasone, dexchlorpheniramine maleate, dexpanthenol,dextroamphetamine, dextromethorphan, diazepam, diazoxide, dibucaine,diclofenac epolamine, dichlorphenamide, dicloxacillin sodium,dicyclomine, dienestrol, diethylpropion hydrochlorid,diethylstilbestrol, diflunisal, digitalis, dicoumarol, digitoxin,digoxin, dihydroergotamine, dihydrostreptomycin, dihydrotachysterol,dihydroxyaluminium amino acetate, dihydroxyaluminium sodium carbonate,diltiazem hydrochloride, dimenhydrinate, dimercaprol, diphenhydraminehydrochloride, diphenoxylate hydrochloride, diphteria antitoxin,dipyridamole, disopyramide phosphate, disulfiram, dobutaminehydrochloride, docusate calcium, docusate sodium, dopaminehydrochloride, doxepin hydrochloride, doxycycline, doxycycline hyclate,doxylamine cuccinate, dronabinol, droperidol, drotaverine,dydrogesterone, dyphylline, guaifenesin, enalapril maleate, analaprilat,ephedrine, epinephrine, equilin, ergocalciferol, ergoloid mesylates,ergonovine maleate, ergotamine tartrate, erythrityl tetranitrate,erythromycin, estradiol, estriol, estrogene, estrone, estropipate,ethcrynic acid, ethambutol hydrochloride, ethchlorvynol, ethinylestradiol, ethionamide, ethopropazine hydrochloride, ethotoin,ethynodiol diacetate, etidronate disodium, etoposide, eugenol,famotidine, fentanyl, fenoprofen, ferrous fumatate, ferrous gluconate,ferrous sulfate, flucytosine, fludrocortisone acetate, flunisolide,fluocinolone acetonide, fluocinonide, fluorescein sodium,fluorometolone, fluorouracil, fluoxymesterone, fluphenazine,flurandrenolide, flurazpam, flurbiprofen, folic acid, furazolidone,flunitrazepam, furosemide, gemfibrozil, gentamicin, gentian violet,glutarate, glutethimide, glycopyrrolate, chorionic gonadotropin,gramicidin, griseofulvin, guaifenesin, guanabenz, guanadrelsulfate,halazone, haloperidol, haloprogin, halothane, heparin calcium, hepatitisvirus vaccine, hetacillin potassium, hexylresorcinol, histaminephosphate, histidine, homatropine, histoplasmin, hydralazinehydrochloride, hydrochlorothiazide, hydrocodone bitartrate,hydrocortisone, hexobarbital, hydroflumethiazide, hydromorphonehydrochloride, hydroquinone, hydroxocobalamin, hydroxyamphetamine,hydroxychloroquine sulfate, hydroxyprogesterone caproate, hydroxyurea,hydroxine hydrochloride, hydroxine pamoate, hyoscyamine, hyoscyaminesulfate, ibuprofen, ifosfamide, imipramide, imipramide hydrochloride,indapamide, indomethacin, insulin, inulin, ocetamid, iodoquinol,iohexol, iopamidol, ipecac, ipodate calcium, ipodate sodium,isocarboxacid, isoetharine hydrochloride, isoflurane, isoniacid,isopropamide iodine, isoproterenol hydrochloride, isosorbide dinitrate,isotretenoin, isoxsuprine hydrochloride, kanamycin sulfate, ketoprofen,ketoconazole, labetalol hydrochloride, lanolin, leucine, leucovorincalcium, levamisole hydrochloride, levocamithine, levodopa,levonorgestrel, levorphanol tartrate, levothyroxine sodium, lidocaine,lincomycin hydrochloride, lindane, liothyronine sodium, liotrix,lisinopril, lithium carbonate, loperamide hydrochloride, loracarbef,lonetil, lorazepam, lovastatin, loxapine, lysine, mafenide acetate,magaldrte, magnesium carbonate, magnesiumchloride, magnesium gluconate,magnesium oxide, other magnesium salts, malathinon, manganese salts,manganese, maprotiline hydrochloride, mazindol, measle virus vaccine,mebendazole, mebrofenin, mecamylamine hydrochloride, meclizinehydrochloride, meclocycline, meclofenamate sodium, medroxyprogesteroneacetate, mefenamic acid, megestrol acetate, meglumine, melphalan,menadiol sodium diphosphate, menadione, menotropine, meperidine,mephenytoin, mephobarbital, meprednisone, meprobaamate, mercaptopurine,mesoridazine besylate, mestranol, metaproterenol sulfate, metaraminolbitartrate, methacycline hydrochloride, methadone hydrochloride,methamphetamine hydrochloride, methazolamide, methdilazine, methenamine,methicillin sodium, methimazole, methionine, methocarbamol,methotrexate, methoxsalen, methoxyflurane, methsuximide,methyclothiazide, methylbenzethonium chloride, methyldopa,methylergonovine maleate, methylphenidate hydrochloride,methylprednisolone, methyltestosterone, methysergide maleate,metoclopramide, metolazone, meoprolol tartrate, metronidazole,metyrapone, metyrosine, mexiletine hydrochloride, mexiletinehydrochloride, miconazole, minocycline hydrochloride, minoxidil,mitomycin, mitotane, molindone hydrochloride, monobenzone, morphinesulfate, mupirocin, medazepam, mefruside, methandrostenolone,methylsulfadiazine, nadolol, nafcillin, nafcillin sodium, nalidixicacid, nalorphine, naloxone, nandrolone decanoate, nandrolonephenpropionate, naproxen, natamycin, neomycin, neomycin sulfate,neostimine bromide, niacin, nitrofurantoin, nalidixic acid, nifedipine,nitrazepam, nitrofurantoin, nitroglycerine, nitromerson, nizatidine,nonoxynol-9, norethindrone, norethindrone acetate, norfloxacin,norgestrel, nortriptyline hydrochloride, noscapine, novobiocin sodium,nystatin, opium, oxacillin sodiumn, oxamniquine, oxandrolone, oxazepam,oxprenolol hydrochloride, oxtriphylline, oxybenzone, oxybutyninchloride, oxycodone hydrochloride, oxycodone, oxymetazolinehydrochloride, oxymetholone, oxymorphone hydrochloride, oxyphenbutazone,oxytetracycline, padimate, panreatin, pancrelipase, papain, panthenol,papaverin hydrochloride, parachlorophenol, paramethasone acetate,paregoric, paromomycin sulfate, penicillamine, penicillin, penicillinderivatives, pentaerythritol tetranitrate, pentazocine, pentazocinehydrochloride, pentazocine salts, pentobarbital sodium, perphenazine,pertussis, phenacemide, phenazopyridine hydrochloride, phendimetrazinetartrate, phenelzine sulfate, phenmetrazine hydrochloride,phenobarbital, phenophtalein, phenoxybenzamine hydrochloride,phentermine hydrochloride, phenylalanine, phenylbutazone, phenylephrinehydrochloride, phenylpropanolamine hydrochloride, physostigmine,phytonadione, pilocarpine, pimozide, pindolol, piperazine, piroxicamplicamycin, poliovirus vaccine inactivated, polycarbophil, polymycin bsulfate, polythiazide, potassium chloride, potassium citrate, potassiumcluconate, potassium iodine, potassium sodiumn tartrate, povidoneiodine, pralidoxime chloride, pramoxine hydrochloride, pramezam,prazepam, praziquantel, prazosin hydrochloride, prazosin hydrochloride,prednisolone, prilocaine, primaquine, primidone, probenecid, probucol,procainamide hydrochlorid, procaine hydrochloride, procarbacinehydrochloride, prochlorperazine, prochlorperazine maleate, procyclidinehydrochloride, progesterone, proline, promazine, promazinehydrochloride, promazine, promethazine, promethazine hydrochloride,propafenone hydrochloride, propantheline, proparacaine hydrochloride,propoxycaine hydrochloride, propoxyphene hydrochloride, propoxyphenenapsylate, propanolol hydrochloride, propyliodone, propylthiouracil,propylthiouracil, protriptyline hydrochloride, pseudoephedrinehydrochloride, pumice, pyrantel pamoate, pyrazinamide, pyrethrumextract, pyridostigmine bromide, pyridoxine hydrochloride, pyrilaminemaleate, pyrimethamine, pyroxylin, pyrvinium pamoate, phenacetin,phenytoin, prednisone, uinidine gluconate, quinidine sulfate, rabiesvaccine, racepinephrine ranitidine, rauwolfia serpentina, resorcinol,ribavirin, riboflavin, rifampin, ritodrine, rubella virus vaccine,saccharin, saccharin sodium, salicylamide, salicylic acid, salsalata,scopolamine, secobarbital sodium, selenius acid, selenium sulfate,sennaserine, simethicone, sodium ascorbate, sodium bicarbonate, sodiumfluoride, sodium gluconate, sodium iodide, sodium lactate, sodiumnitrite, sodium ditroprusside, sodium salicylate, spironolactone,stannozolol, streptomycin, sucralfate, sulfacetamide, sulfadiazine,reserpine, sulfadioxine, sulfamerazine, sulfamethazine, sulfamethizole,sulfamethoxazole, sulfamethoxydiazine, sulfapyridin, sulfasalazine,sulfaperin, sulfathiazole, sulfisoxazole, sulfinpyrazone, sulindac,suprofen, stilains, tamoxifen citrate, taurine, temacepam, terbutalinesulfate, terfenadine, terpin, testolacton, testosterone, tolazamide,tolbutamide, tetracaine, tetracycline, tetrahydrocycline, theophylline,thiabendazole, thiamine hydrochloride, thiamin, thiamylal,thiethylperazine thimerosal, thioguanine, thioridazine hydrochloride,thistrepton, thiotepa, thiothixene, threonine, thyroid, ticarcillin,timolol, tioconazole, titaniumdioxide, tutanium powder, tolazamide,tolbutamide, tolmetin, tolnaftate, trazodone hydrochloride, tretinoin,triacetin, triamcinolone, triamterene, triazolam, trichorfon,trichlonnethiazide, trientine hydrochloride, trifluoperazinehydrochloride, triflupromazine, trihexyphenidyl hydrochloride,trimeprazine tartrate, trimethadione, trimethobenzamide hydrochloride,trimethoprim, trioxsalen, tripelennamine, triprolidine,trisulfapyrimidine, tropicamide, trypsin, tryptohan, tuberculin,tyloxapol, tyropanoate sodium, tyrosine, tyrothricin, thyrothricinbethamethasone, thiotic acid, sotalol, salbutamol, norfenefrine,silymarin, dihydroergotamine, buflomedil, etofibrate, indometacin, urea,valine, valproic acid, vancomycin hydrochloride, vasopressin,verapramil, vidarabine, vinblastine, vincristine, vitamins, warfarin,yellow fever vaccine, zinc acetate, zinc carbonate, zinc chloride, zincgluconate, beta acetyl digoxin, piroxicam, haloperidol, ISMN,amitriptylin, diclofenac, nifedipine, verapamil, pyritinol, nitrendipin,doxycycline, bromhexine, methylprdnisolone, clonidine, fenofibrate,allopurinol, pirenyepine, levothyroxin, tamoxifen, metildigoxin,o-(beta-hydroxyethyl)-rutoside, propicillin, aciclovir mononitrate,paracetamol, naftidrofuryl, pentoxifylline, propafenone, acebutolol,L-thyroxin, tramadol, bromocriptine, loperamide, ketotifen, fenoterol,cadobelisate, propanolol, enalaprilhydrogen maleate, bezafebrate, ISDN,gallopamil, xantinol nicotinate, digitoxin, flunitrazepam, bencyclane,dexapanthenol, pindolol, lorazepam, diltiazem, piracetarn,phenoxymethylpenicillin, furosemide, bromazepam, flunarizin,erythromycin, metoclopramide, acemetacin, ranitidin, biperiden,metamizole, doxepin, dipotassium chloroazepate, tetrazepam, estramustinephosphate, terbutaline, captopril, maprotiline, prazosin, atenolol,glibenclamide, cefaclor, etilfrine, cimetidine, theophylline,hydromorphone, ibuprofen, primidone, clobazam, oxaceprol,medroxyprogesterone, flecainid, pyridoxal-5-phosphate glutaminate,hymechromone, etofylline clofibrate, vincamine, cinnarizine, diazepam,ketoprofen, flupentixol, molsimine, glibornuride, dimetinden, melperone,soquinolol, dihydrocodeine, clomethiazole, clemastine, glisoxepide,kallidinogenase, oxyfedrine, baclofen, carboxymethylcysteine,thioridazine, betahistine, L-tryptophan, murtol, bromelaine,prenylamine, salazosulfapyridine, astemizol, sulpiride, benzerazide,dibenzepine, acetylsalicylic acid, miconazol, nystatin, ketoconazole,sodium picosulfate, coltyramine, gemfibrocil, rifampicin, fluocortolone,mexiletin, amoxicillin, terfenadrin, mucopolysaccharide polysulfade,triazolam, mianserin, tiaprofenic acid, amezinium metilsulfate,mefloquine, probucol, quinidine, carbamazepine, L-aspartate, penbutolol,piretanide, aescin amitriptyline, cyproterone, sodium valproinate,mebeverine, bisacodyl, 5-aminosalicylic acid, dihydralazine, magaldrate,phenprocoumon, amantadine, naproxen, carteolol, famotidine, methyldopa,auranofme, estriol, nadolol, levomepromazine, doxorubicin, medofenoxate,azathioprine, flutamide, norfloxacin, fendiline, prajmalium bitartrate,lipid derivatives of phosphonatides, amphiphilic polymers, adenosinederivatives, sulfated tannins, monoclonal antibodies, and metalcomplexes of water soluble texathyrin.

Representative nutraceutical agents include components which promote orprevent disease or enhance well-being such as antioxidants,phytochemicals, hormones, vitamins such as Vitamin C and Vitamin E,pro-vitamins, minerals, microorganisms such as bacteria, fungi andyeast, prebiotics, trace elements, essential and/or highly unsaturatedfatty acids such as omega-3 fatty acids and mid-chain triglycerides,nutritional supplements, enzymes, pigments, oligopeptides, dipeptidesand amino acids.

The active ingredient may also be a protein, an enzyme, a peptide, apolysaccharide, a nucleic acid, a cell fragment, a biologically activesubstance, a salt, or the like. The active agent may also be a lipidsuch as, but not limited to, fat-soluble vitamins (e.g., vitamins A, D,E and K), ceramides in which the fatty acid components may be one ormore of the following: alpha-hydroxy 6-hydroxy-4-sphingenine,alpha-hydroxy phytosphingosine, alpha-hydroxy sphingosine, ester linkedomega-hydroxy 6-hydroxy-4-sphingenine, non-hydroxy phytosphingosine,non-hydroxy sphingosine, and/or ester linked omega-hydroxysphingosineand free sterols.

The active ingredients may have cosmetic properties such as, but notlimited to: moisturizing and/or humectant, dermatological, self-tanning,anti-allergenic, anti-hair re-growth, anti-acne and/or seboregulator,anti-ageing, anti-dandruff, antimicrobial, antioxidant,antiperspirant/deo-active, antipuffing, antistatic, anti-stretch marks,anti-tartar, anti-wrinkle, astringent, conditioning, cooling, complexingand sequestering, depilatory, depigmentors, draining, dyes, emollient,exfoliating, firming/botox-like, foaming, hair growth, healing, heating,insects repellents, lightening/whitening, myorelaxing, natural sunprotector, nourishing, protective, perfumes, pearlescent agents, plantextracts, purifying, radiance, rebalance, refreshing,regenerating/revitalizing, repairing, restructuring/replenishing,softener, shining, slimming, smoothing, soothing, tensing,toning/invigorating, venotonic, vitamins etc.

The active ingredient may also counteract cellulite, counteract the lossof hair, decrease fat deposition, treat discoloring of the skin, modifyaspects of a body part, muscle toner, skin or hair, may preventcavities, prevent or treat dental plaque, prevent redness/anti-rosacea,or the like.

Non-limiting examples of cosmetic agent include: glycerin, lactic acidand/or lactates, sodium lactate, butylene glycol, propylene glycol,biosaccaride gum-1, glycine soy, ethylhexyloxyglycerin, pyrrrolidone,carboxylic acid, hyaluronic acid, chitosan, fucose-rich polysaccharide,vitamins A, B₁₋₆, B₁₂, C, D, E, F, H, K, and PP, as well as theirderivatives, retinyl palmitate, ascorbyl glucoside, tocopheryl acetate,tocopheryl palmitate, niacinamide, panthenol, alpha-lipoic acid,phytoene, D-biotin, coenzyme Q10, alpha-glucosylrutin, carnitine,carnosine, natural and/or synthetic isoflavonoids, creatine, creatinine,lignans, taurine, and/or b-alanine, panthenol, allantoin, tannin, andplant active ingredients, such as azulene and bisabolol, glycyrrhizin,hamamelin and plant extracts, such as camomile, aloe vera, hamamelis,and liquorice.

The formulation may also comprise irritation-mitigating additives tominimize or eliminate the possibility of skin irritation or skin damageresulting from the active ingredient or other components of theformulation. Suitable irritation-mitigating additives include, forexample: alpha-tocopherol; monoamine oxidase inhibitors, particularlyphenyl alcohols such as 2-phenyl-1-ethanol, glycerin, salicylic acidsand salicylates, ascorbic acids and ascorbates, ionophores such asmonensin, amphiphilic amines, ammonium chloride, N-acetylcysteine,cis-urocanic acid, capsaicin, and chloroquine.

In a specific, but non-limiting example, the active ingredient may havedeodorizing properties and/or scents such as deodorants, fragrances orperfumes that are used to mask odorS or replace an unwanted odor with amore desired one. As used herein, deodorizing agents include agents thatcapture and remove smells from the surrounding air or object or skin.Representative examples of the deodorizing agents include pine oil,activated charcoal and aqueous solutions containing chlorine, glyoxal,glycol, zeolite, silica, quartz diorite-porphyrite, and/or calciumchloride. The deodorizing agent may be used to remove one or moreunwanted smells from an area, such as those of human sweat caused byodor-causing microbes on the skin, hydrogen sulfide, animal hair anddander, cigarette smoke.

A fragrance include aqueous solutions made from, but not limited to, thefollowing ingredients or combinations thereof: aromatic compounds madefrom fragrant essential oils, such as those made from plants like rose,jasmine, lavender; fruits, such as oranges, lemons and limes; leaves,such as sage and rosemary; seeds, such as the cocoa bean, corianderseed, cardamom seed and anise seed; woods, such as those from pine, fir,and sandalwood trees; seaweed; lichens or moss, or the like. Thefragrance is generally used to give the surrounding air or selectedobjects a particular desired smell that can be used to mask other odorsor scents or add to the surrounding area a desirable scent. In someimplementations, the active ingredient may be a combination of adeodorizing agent and a fragrance.

In a further, but non-limiting example, the active ingredient may alsobe suitable for the reduction and potential blocking of UV rays toexposed skin. As used herein, a sunscreen (also referred to as sunblock) include topically applied compound that reduces or reflects(blocks) certain wavelengths of the ultraviolet (UV) spectrum insunlight, specifically UV-A rays in the 400 nm to 315 nm spectrum andUV-B rays in the 315 nm to 280 nm spectrum. Long-term exposure (whichvaries with the strength of sunlight) to these wavelengths may causesunburn and may also contribute to the onset and development of certainserious conditions and types of cancer, most notably the skin cancermelanoma.

Representative examples of agents in sunscreen include p-aminobenzoicacid (PABA), padimate O-phenylbenzimidazole sulfonic acid, cinoxate,dioxybenzone, oxybenzone homosalate, methyl anthranilate, octocrylene,octyl methoxycinnamate, octyl salicylate, sulisobenzone, trolaminesalicylate, avobenzone, ecamsule, titanium dioxide, and zinc oxide.

Representative agents that may treat the effects of sunburn typicallyinclude cream or gel solution of aloe vera, vitamin E, andhydrocortisone. Another variant on the above method for using the activeingredient may also conceivably deliver agents that tint the skin with aparticular shade, color or hue that mimics the effect of exposure to thesun (this is commonly referred to as a “sunless tan”). Representativeagents that may deliver a “sunless tan” include dihydroxyacetone (DHA),erythrulose, and canthaxanthin.

Active ingredients may also have cleansing or detoxifying properties.Representative examples of such active ingredients include disinfectantssuch as chlorohexidine gluconate, cetramide, benzylknium chloride orpeptides such as polymixin B.

In specific, but non-limiting examples, some active ingredients may beused to achieved the following results: shea butter may be used tohydrate or heal the skin; caffeine may be used to remove fat; mangobutter may be used to moisturize skin; green tea may be used tostimulate; vitamin A palmitate may be used as an anti-aging agent or asan anti-oxidant agent; vitamin C palmitate may be used as an anti-ageingagent, an anti-oxidant agent, for whitening the skin; wheat cerasomepowder may be used as an anti-aging agent; glycerrhizinic acid may beused as an anti-inflammatory agent, as a calming agent or a revitalizingagent; cococin may be used to improve hair growth, cell growth and bloodcirculation; ursolic acid may be used to increase collagen levels;venocin may be used to improve blood circulation and scaring; vitacellpowder may be used as a tonic or a detoxifying agent. Such agents mayalso be used in combination such as, for example, venocin or cococin maybe combined to caffeine to treat cellulites; venocin, vitacell andminerals may be combined to be used as a toner.

Other active ingredients may include: aluminum trihydrate as a fireretardant, astringent; acediasulfone as a antibacterial; agaricic acidas a antiperspirant; alclometastone as a topical anti-inflammatory;calcium alginate as a topical hemostatic; amidomycin as a fungicide;antimony oxide as a fire retardant; apigenin as a yellow dye, mordant;aspirin as an anti-inflammatory, antipyretic; azanidazole as aantiprotozoal (trichomonas); azelaic acid as a antiacne; baicalein as anastringent; bendazac as an anti-inflammatory; benomyl as a fungicide,ascaricide; benzestrol as estrogen; benzylpenicillinic acid as anantibacterial; benzylsulfamide as an antibacterial; bergaptene as anantipsoriatic; betasine as an iodine source; bezitramide as a narcoticanalgesic; bibrocathol as a topical antiseptic; bietanautine as anantihistaminic; bifenox as a herbicide; bifonazole as an antifungal;binapacryl as a fungicide, miticide; bis(p-chlorophenoxy) methane as amiticide; bismuth aluminate as an antacid; bismuth iodide oxide as ananti-infective; bismuth phosphate as an antacid, protectant; bismuthsubcarbonate as a topical protectant; bismuth subgallate as anastringent, antacid, protectant; bisphenol A as a fungicide; bitertanolas an agricultural fungicide; bithionol as a topical anti-infective;bromacil as an herbicide; bromadiolone as a rodenticide; bromcresolgreen as an indicator; bromcresol purple as an indicator; bromethalinlinas a rodenticide; p-bromoacetanilide as an analgesic, antipyretic;3-bromo-d-camphor as a topical counterirritant; bromophos as aninsecticide; bromopropylate as an acaricide; 5-bromosalicyl-hydroxamicacid as an antibacterial (tuberculostatic); 5-Bromosalycilic acidacetate as an analgesic; bromosaligenin as an anti-inflammatory;bromthymol blue as an indicator; broxyquinoline as an antiseptic,disinfectant; bucetin as an analgesic; bumadizon as an analgesic,anti-inflammatory, antipyretic; bupirimate as a fungicide; busulfan asan insect sterilant, antineoplastic; butamben as a topical anesthetic;butrylin as an insecticide; butylated hydroxy anisole as an antioxidant(BHA); butyl paraben as a pharmaceutic aid, food preservative;4-tert-Butylphenyl salicylate as a light absorber; cacotheline as anindicator; cactinomycin as an atineoplastic; cadmium salycilate as anantiseptic; calamine as a skin protectant; calcium carbonate as anantacid; calcium saccharate as a pharmaceutic aid; calcium tartrate as apreservative, deodorant, antacid; cambendazole as an anthelminthic,candicidin as a topical antifungal; candidin as a topical antifungal;capsaicin as a topical analgesic; captan as a fungicide, bacteriostat;carbadox as an antimicrobial; carbamazepine as an anticonvulsant,analgesic; carbarsone as an antiamebic; carbaryl as a contactinsecticide; carbazochrome salycilate as an antihemorrhagic; carbendazimas a fungicide; carbophenothion as a miticide, insecticide; carboquoneas an antineoplastic; carisoprodol as a skeletal muscle relaxant;carthamin as a dye; carvacrol as a disinfectant; cephalin as a localhemostatic; chalcomycin as an antibiotic; chartreusin as an antibiotic;chitin as a vulnerary; chloramben as an herbicide; chloramphenacolpalmitate as an antimicrobial; chloranil as a fungicide; chlorbetamideas an antiamebic; chlordimeform as an insecticide; chlorfenac as anherbicide; chlorfenethol as an acaricide; chlorhexidine as a topicalantibacterial; chloroazodin as an antibacterial, topical anesthetic;chlorophacinone as an anticoagulant rodenticide; p-chlorophenol as anantiseptic; chlorothricin as an antibiotic; chlorotrianisene asestrogen; chloroxylenol as an antiseptic, germicide; chlorphenesin as atopical antifungal; chlorphenesin carbamate as a relaxant (skeletalmuscle); chlorphenoxamide as an antiamebic; chlorpropamide as anantidiabetic; chlorpyrifos as an insecticide; chlorquinaldol as atopical antibacterial; chlorsulfuron as an herbicide; chlorothion as aninsecticide; chlozoxazone as a relaxant; cholesterol as a pharmaceuticaid; chromic carbonate as a pigment; chromic hydroxide as a pigment;chromic oxide as an abrasive; chromic phosphate as a green pigment;chrysarobin as an antipsoriatic; cilastazol as an antithrombotic;cinoxate as a sunscreen agent; ethylenediaminetetraacetic acid (EDTA) asan odor absorbent; disodium salt of EDTA as a chelator; sodiumbicarbonate as an odor absorbent/pH modifier; acarbose as anantidiabetic; acefylline piperazine as a bronchodilator; acenocoumarol,sodium salt as an anticoagulant; acephate as an insecticide;acetaminophen as an analgesic; acetylleucine as an antivertigo agent;monoethanolamine acid Violet 7B as a dye/stain; acitretin as anantipsoriatic; acranil as an antiprotozoal (Giardia); acriflavine as ananti-infective; actaplanins as a growth stimulant; algestoneacetophenide as an antiacne; algin as an hemostatic; almagate as anantacid; (−)-ambroxide as a fragrance; ambucaine hydrochloride as alocal anesthetic; amodiaquin as an antimalarial; anabasine hydrochlorideas an insecticide; o-anisaldehyde as a fragrance; anisomycinhydrochloride as a topical antitrichomonal; aralkonium chloride as anantiseptic, germicide; asiaticoside as a dermatide, wounds, burns;bebeerine as an antimalarial; potassium benzoate as a preservative,antifungal; benzoyl peroxide as a dermatide, antiacne; benzylideneacetone as a fragrance; bidrin as an insecticide; biphenaminehydrochloride as an antiseborrheic; bishydroxycoumarin as ananticoagulant; bismuth tribromophenate as a topical antiseptic;blasticidin S hydrochloride as an antimicrobial; bromocresyl as a greenindicator; bromophenol blue as an indicator; butathamine hydrochlorideas an anesthetic; calcium ascorbate as Vitamin C/calcium source; calciumbisulfite as a germicide; calcium thioglycollate as a depilatory;carbowax as an ointment base; cetalkonium chloride as an antibacterial;cethoxonium bromide as an antiseptic; chartreusin as anantimycobacterial; chloramine-T as a topical antiseptic; cinnamic acidas a fragrance; cotarnine chloride as an hemostatic; demercarium bromideas a topical antiglaucoma; D-2-deoxyribose for DNA synthesis;dequalinium chloride as an antiseptic; dermostatin as an as an indicatorof nitrates/nitrites; diamthazole dihydrochloride as an antifungal;dibekacin sulfate as an antibacterial;3,5-Dibromo-4-hydroxybenzenesulfonic acid sodium salt as a topicaldisinfectant; dibromopropamidine as a cosmetic preservative; diflorasoneas a topical anti-inflammatory; dihydroxyacetone as an artificialtanning agent; diisobutyl sodium sulfosuccinate as a wettingagent/detergent; dimethisoquin as a topical anesthetic; diphenicillinsodium as an antibacterial; diphetarsone as an antiamebic; dipyrone asan analgesic, antipyretic; diquat dibromide as a defoliant; domiphenbromide as a topical anti-infective; ecognidine as a topical anesthetic;edetic acid as an antioxidant; edoxudine as an antiviral; endothal as adefoliant; eosine as a yellowish cosmetic dye; esculin as a skinprotectant; ethacridine as an antiseptic; euprocin dihydrochloride as atopical anesthetic; fenticonazole nitrate as a topical antifungal;fortimicin(s) as an antibacterial; fungichromin as a topical antifungal;gallic acid as an astringent, styptic; gentian violet as a topicalanti-infective; gluconolactone as a cleaner; gossypol as a rubberantioxidant; heparin as an anticoagulant, hexamethylolmelamine as afireproofing agent; mexamidine as an antiseptic, anti-acne; hydroquininehydrochloride hemihydrate as a depigmentor;1-(Hydroxymethyl)-5,5-dimethylhydantion as a cosmetic preservative;8-Hydroxyquinoline sulfate as an antiperspirant, deodorant; iodic acidas an astringent; itraconazole as an antifungal; kanamycin(s) as anantibacterial; lactic acid as an acidulent; meralein sodium as a topicalanti-infective; titanium powder or else as a muscle toner; ceramicpowder or else as a temperature regulator; peppermint or menthol orderivatives thereof as a cooling agent; taurine as a stimulant; etc.

The active ingredients may be in the form of a formulation, acomposition, a mixture, a preparation, a composite, a solution, apowder, a crystal or the like.

In a particular, but non-limiting implementation, the active ingredientis mixed with the other elements of the formulation, preferably prior tothe formation of microparticles. Active ingredients having differentproperties may be added to the same formulation. Microparticles obtainedfrom such a formulations will have a mix of the different activeingredients dispersed therein.

The active ingredient and the other elements of the formulation may beseparable and uncompounded with each other. Alternatively, the activeingredient and the other elements of the formulation may be chemicallybounded or may chemically interact. The types of possible interactionsbetween the active ingredient and the other elements of the formulationsdepend, in part, on the nature of the active ingredient and the natureof the elements of the formulations.

The formulation may be homogenous or heterogeneous. A homogenousformulation includes a formulation of two or more substances that cannotbe readily separated by common physical means (such as, for example,setting, filtration, etc). A heterogeneous formulation includes aformulation of two or more substances that can be readily separated bycommon physical means (such as, for example, setting, filtration, etc).

The active ingredient may be uniformly or a non-uniformly distributedwithin the microparticles. When the active ingredient is uniformlydistributed in the microparticle, the concentration of active ingredientin the microparticle is steady as the microparticle disintegrates,whereas when the active ingredient is not uniformly distributed withinthe microparticle, the concentration of the active ingredient in themicroparticle varies as the microparticle disintegrates. In other timerelease situations, the concentration of the active ingredient increasestowards the center of the microparticle to compensate for reducedsurface area as the microparticle disintegrates and thus tend tocounteract the reduction of the rate of release of the active ingredientowing to the reduction of the surface area of the particle (as theparticle shrinks due to erosion, its surface area diminishes).

The active ingredient may be hydrophobic or hydrophilic; preferably, theactive ingredient is hydrophobic. In formulations where the activeingredient is not miscible with the carrier material, the activeingredient may, for example, be encapsulated in a material that isitself miscible with the carrier material so that the encapsulatedactive ingredient can be incorporated in the microparticles. Forexample, to incorporate a hydrophilic active ingredient in amicroparticle composed primarily of a hydrophobic carrier material, itmay be advantageous to encapsulate the hydrophilic active ingredient ina substance that is miscible with the hydrophobic carrier material ofthe microparticle. Examples of such substance include, but are notlimited to, biocompatible polymers, such as polyethylene glycol; andamphipathic compounds such as soaps and detergents.

In a specific, but non-limiting implementation, the active ingredient issuitable for topical application and/or transdermal administration to asubject.

IV. Vehicles for Application of Formulations Comprising Microparticles

As intended by the present invention, application vehicles are usefulfor storage, transport and/or application of the microparticles. Theapplication vehicle may for example, be a liquid body, a cream, a paste,a gel, a foam body or the like.

Preferably, the nature of the application vehicles is compatible withthe composition of the microparticle as well as with the substrate ontowhich the microparticles are to be applied so as to avoid deterioration,degradation or weakening of the microparticles and/or substrate and/orany active ingredient that may be dispersed within the microparticles,and/or to avoid any other undesirable effects.

The amount of microparticles in the application vehicle may influencethe state of the vehicle, i.e., whether the vehicle is a liquid, apaste, etc. The amount of microparticles also influences the viscosityof the vehicle, for example, the concentration of microparticles in aliquid vehicle is such that the viscosity of the liquid vehicle allows asubstrate such as, for example, a textile, to be readily immersed intothe liquid vehicle having the microparticles. The concentration ofmicroparticles in a cream, gel or paste vehicle is such that theviscosity of the cream, gel or paste vehicle does not permit to readilyimmerse the substrate into the gel or paste vehicle but allows for thedirect application of the vehicle onto the substrate such as, forexample, by coating or spreading the application vehicle onto thesubstrate. Application of a cream, gel or paste vehicle to a substratemay be done using, for example, a knife, a blade, a Meyer Rod or may bedone by rolling the application vehicle onto the substrate such as afoam sheet via, for example, a roller, or by direct application with theuse of an analog roller, or serigraphy instrumentation or Flexoinstrumentation or precision spray or deposit nozzles.

Ancillary agents may also be present in the application vehicle tofacilitate the storage, transport and/or application of the applicationvehicle/microparticles as well as to facilitate or improve the activityor property of the active ingredient. Such ancillary agents may include:dies, antiseptic agents, anti-fungic agents, antibiotics, wettingagents, agents for hydrophobic treatment, surfactants, preservatives,color retention agents, emulsifiers, humectants, foaming/anti-foamingagents, anti-coagulating agents, stabilizers, antioxidants (to preventoxidization), pharmaceutically acceptable carriers, diluents,excipients, among others.

In some implementations, the formulation from which the microparticlesare obtained acts as the application vehicle. In these specificimplementations, the formulation acting as application vehicle is theformulation not forming part of the microparticles.

In a specific, but non-limiting implementation, the application vehicleis applied to a support. As used herein, the term “support” includesapplicators that may be used to transfer the formulation ofmicroparticles to a substrate, wherein the substrate include an articleof manufacture, the skin, etc. The support may be flexible,semi-flexible or non-flexible.

The surface of the support may be embossed, may have raised patterns,may have recesses or holes defined therein into which the formulationmay be applied, such as, for example a polyethylene film embossed with apattern such as a diamond pattern.

The support may be, for example, a polymer, more particularly apolyolefin, a foam, a non-woven material, a woven material, a paperrelease composition, a resin, a glass fiber, a carbon fiber, as well asknown ductile metals such as aluminum, stainless steel, copper, silveror gold, or any combination thereof.

In a specific, but non-limiting, implementation, the application vehicleis applied to a polypropylene (also referred to herein as PPFV) support(FIG. 10A, element 1002) on which, for example, a square pattern ofglass fiber has been applied (FIG. 10A, element 1000), thereby definingembossment and recesses on the surface of the polypropylene. Theapplication vehicle may be prepared at a concentration of microparticleswhich is lower than the final concentration of microparticles desired.The application vehicle is applied to the PPFV so as to fill therecesses created by the pattern or glass fiber. The applicationvehicle/PPFV is then partially dried to evaporate part of the water fromthe application vehicle after which step, more application vehicle maybe applied. This type of transfer is referred to herein as “humidtransfer”, where some water is transferred to the substrate. Theresulting treated PPFV may be pressed against a substrate, such as forexample a textile, to transfer the formulation of microparticles ontothe substrate (FIG. 10B, element 1004).

It is also possible to let the treated PPFV dry completely so as totransfer very low water to the support. This type of transfer isreferred to herein as “dry transfer”, where very little or no water istransferred to the substrate. This type of transfer may be facilitatedby the application of heat or ventilation. However, if heat is to beused, it should be carefully applied so as to prevent premature meltingof the microparticles.

As used herein, the term “treated” refers to a material, a support, asubstrate, an article, a textile, a fabric, etc. having the formulationsand/or the microparticles as defined herein applied thereon. A treatedmaterial, support, substrate, article, textile, fabric, etc. hasformulations and/or microparticles distributed therein.

As used herein, the term “distributed” includes microparticles that areretained in the pores or interstice of the material, support, substrate,article, textile, fabric, etc.; includes microparticles that areattached or fixed to the material, support, substrate, article, textile,fabric, etc.; and includes microparticles that have been absorbed by thematerial, support, substrate, article, textile, fabric, etc., and whichupon being absorbed may or may not retain the microparticle shape.

V. Substrate

As used herein the term “substrate” includes materials onto which theformulation and/or microparticles are applied and from which themicroparticle/active ingredient are released. Preferably, the substrateis porous. A porous substrate refers to a substrate that hasinterstices, recesses, pores or cross linkage openings in which themicroparticles can be retained, impregnated or trapped. The interstices,recesses or cross linkage openings are preferably of a dimension thatpermits insertion and/or retention of the microparticles.

In some implementations of the present invention, the substrate is theskin of a human or an animal.

Specific examples of suitable substrates include, but are not limitedto, fibrous textiles including natural fibers either vegetal (e.g.,cotton, linen, jute) or animal (e.g., wool and silk) as well as mineralfibers (e.g., asbestos and viscose); chemical fibers either synthetic orartificial like polyester, nylon, acetate, polypropylene and rayon;paper and paper products; product made from composites; products madefrom wood or wood by-products, such as furniture materials and doors;products made from carbon fiber, products made from glass fiber,synthetic foam, such as polyethylene, polystyrene and polyurethane foam.Textiles may be woven, knitted or machine-knitted, or be present as acomposite material (non-woven textile). In the case of compositematerials, the fabric is not produced by wrap and weft or stitchformation, but by interlocking and/or cohesive and/or adhesive bondingof textile fibers. Non-woven fabrics are loose materials produced fromspun fibers or filaments, in most cases made of polypropylene, polyesteror viscose, the cohesion of which is generally provided by the fibersintrinsically holding together. In this regard, the individual fibersmay have a preferred orientation (oriented or cross-laid non-wovenfabrics), or be unoriented (entangled non-woven fabrics). The non-wovenfabrics may be mechanically bonded by needle punching, stitching, orentangling by means of strong water jets. Adhesively bonded non-wovenfabrics are produced by gluing the fibers together with liquid bindingagents (for example, acrylate polymers, SBR/NBR, polyvinyl ester,polyurethane dispersions), or by melting or dissolving so-called binderfibers that are added to the non-woven fabric during its production.Non-woven material may be obtained from, for example, viscose, cotton,cellulose, jute, hemp, sisal, silk, wool, polypropylene, polyester,polyethylene terephthalate (PET), aramide, nylon, polyvinyl derivatives,polyurethanes, polylactide, polyhydroxyalkanoate, cellulose estersand/or polyethylene, and also mineral fibers, such as glass fibers orcarbon fibers.

Examples of fabrics also include blends of dual or multiple fibers suchas, but not limited to, polyester/elastane blends, polyamids,polyamide/elastane blends, cotton/polyester/elastane blends,polyacrylonitriles, acetates, modal, lyocell and linens.

Non-limiting examples of substrate onto or into which the formulationand/or microparticles may be applied include: clothing and accessories,bags and suitcases, personal cares, bandages, animal cares, toys,furniture, housing cleansing products, beddings, carpets/rugs, kitchenaccessories, paints/decorations, agro textiles, geo-textiles, paper andpulp, plastic, ceramics, wood, glass, metal, leather, sporting articles,leisure and outdoor articles, tools, protective gears or the like.

The formulations and/or microparticles defined herein may be appliedonto a finished article of manufacture, such as an article of clothing,bedding, etc. However, the formulations and/or microparticles mayalternatively be applied to the material entering into the fabricationof the article of manufacture, prior to its production. For example, theformulations and/or microparticles defined herein may be coated onto athread for sewing or weaving (e.g., a cotton, silk or nylon thread)entering into the fabrication of an article of manufacture (e.g., anarticle of clothing). Additionally, the treated thread may be furthercoated with a protective material to prevent premature release of theactive ingredient. Such protective coating may comprise, for example, awax component.

VI. Application of Microparticles to a Substrate

The type of interactions between the microparticles and the substratecan be of physical, chemical or electrical nature or may be of anycombination thereof. Specific examples include, but are not limited to:

(a) binding of the microparticles to the substrate by means of thebinding agent which has chemical affinity for both;

(b) entrapment of the microparticles within the substrate, facilitatedby physical or non-covalent chemical manipulation of the substratetogether with the microparticles in the presence of the binding agent;and

(c) naturally-occurring chemical affinity which may occur between thesurface of the microparticles and the substrate. These forces includehydrophobic interactions, hydrogen bonding, ionic or electrostaticinteractions.

In one specific aspect, the microparticles are applied to a substrate bytransfer printing. The schematic representation at FIG. 7 illustrateshow a formulation of microparticles may be transferred to a substrateusing transfer printing. In this specific example, the formulation ofmicroparticles (702) may be first applied to a solid support (700). Thisformulation may then be transferred (704) to a substrate (706) such as atextile when the support (700) is pressed against the substrate (706).This technique is well known in the art and is considered a versatileinvention for applying designs to various solid objects.

In another specific, but non-limiting example, the microparticles may beapplied to the substrate by screen-printing. The technique ofscreen-printing includes the technique of reproducing a stencilrepresenting a design (such as a graphic design or logo) to an objectusing a flat screen or a cylinder screen made of a fine, porous fabric.These techniques are also referred to as serigraphy or stencilingmethod.

In this method, a stencil that represents the inverse (or negative)image of the design to be reproduced is created on a screen made of afine, porous fabric that is stretched out over a frame. The stencildefines the areas where the design will not appear on the object to beprinted and an application vehicle/formulation of microparticles asdefined herein is placed on top of the screen, and the mesh openings arefilled with the application vehicle/formulation of microparticles. Anoperator or an automatic system fills then applies the applicationvehicle/formulation of microparticles that is in the mesh openings tothe object and the formulation of microparticles is transferred bycapillary action to the substrate in a controlled and prescribed amountdefined by the thickness of the stencil and the mesh. The frame is thenremoved from the surface of the object, leaving the formulation ofmicroparticles upon its surface in the prescribed design. The techniqueof screen-printing is well known in the art and is known as a versatiletechnology that is used to print designs on a wide variety of objectsincluding shirts, hats, polyethylene, polypropylene, paper, metals,wood, etc. and may be used to apply to a substrate the microparticlesdefined herein.

In a specific but non-limiting example, the microparticles comprising aprescribed pharmaceutical agent (or drug), are printed in a prescribeddesign on a substrate such as, for example, a shirt that can be worn bythose in need of the pharmaceutical agent. By wearing this shirt, thewearer absorbs their prescribed dose of the active ingredient throughthe skin. In this specific example, the microparticles may be suspendedin a liquid or semi-liquid application vehicle that may also be usedsolely or combined with dye or ink to help identify when the dose isexhausted. Each shirt is turned inside out and then put on a supportthat is used to hold the shirt while the liquid application vehicle isbeing applied. Non-permeable material is then applied to a fine mesh ofporous fabric (such as for example, PPFV) stretched over a frame to formthe inverse (negative) image of the design to be printed on the shirt.The application vehicle is then applied to the mesh and a bar is used todistribute the application vehicle along the mesh, filling the spaceswithin the mesh with the application vehicle containing themicroparticles. The frame is then applied to the surface of the shirtand then a spongious material, such as a squeegee (or rubber blade) ispassed over the mesh to force the liquid application vehicle onto thesurface of the shirt. The application vehicle that is contained in themesh openings is transferred to the shirt. The process may be repeatedwith other stencils and application vehicles to apply other designs andother active ingredients to the shirt. Once all designs and allapplication vehicles have been applied, the shirt is then removed fromthe support, dried and then turned inside-out again so that the surfaceof the shirt onto which the liquid material was applied is now on theinside of the shirt and will be physically in contact with the skin ofthe wearer.

The technique of ink-jet printing includes propelling variably sizeddroplets of liquid or melted material (such as dye or ink) onto anobject, fabric or substrate. Unlike the transfer and the screen printingtechniques discussed above, ink-jet printing applies the compound or inkto be printed directly to the material itself, without having totransfer the material to an intermediary, such as a frame. Thistechnique may require a computer to control the ink-jet printingequipment that is used to deliver the ink (or other material) onto thesubstrate according to a certain pattern. This technique is well knownin the art and is known as a very versatile technology that can becheaply and reliably used to print designs on a wide variety ofmaterials, including most paper products, as well as thin fabrics (e.g.,cotton) made of natural or artificial fibers. This technique may also beused to apply the microparticles as defined herein to an object.

The schematic representation of FIG. 8 illustrates an example of how aformulation of microparticles/active ingredients may be transferred to atextile using an ink-jet printer. In this example, the cartridge (802)of the ink-jet printer (800) is filled with the applicationvehicle/formulation of microparticles (804) and is inserted into anink-jet printer that is connected to a computer and controlled by asoftware application running on the computer. The ink-jet printerapplies the application vehicle/formulation of microparticles (804)directly to the surface of the substrate (806) in the prescribed designunder the direction of a software application running on a computer.

In a further aspect, the formulation of microparticles may be applied toa substrate by use of pressing rollers. This technique may be used whereit is necessary to apply the formulation of microparticles consistentlyacross and throughout the substrate, as well as in cases where anearlier usage of the printing technique either did not transfersufficient amounts of the formulation or did not saturate the substratesufficiently.

Another variant on the use of this technique may be seen from theprevious non-limiting example used to illustrate the transfer printingtechnique. In this example, a porous material containing the applicationvehicle is applied against a substrate to transfer the microparticles ina desired design. Additionally, pressing rollers may be used to compressthe porous material onto the substrate under pressure, thus enabling thetransfer of the microparticles onto the substrate.

Pressing rollers could also be used to transfer a predetermined designin a gel form. Pressure is used to release the predetermined design ontoan article of manufacture.

The dose or amount of active ingredient to be applied to a substrate,the distribution of the active ingredient on the substrate, and theperiod of exposure to the active ingredient depend on the effect ormanifestation desired and on the nature of the active ingredient. Thedose, distribution and period of exposure of active ingredient will thusbe apparent to a person skilled in the relevant art.

VII. Release of the Active Ingredient

Microparticles are released from the substrate when the microparticlesare subjected to progressive erosion and/or degradation caused by one ormore stimuli or when the treated substrate is subjected to stimuli thatcause progressive erosion and/or degradation of the microparticles orsimply when the microparticles are detached from the substrate.

The overall physical structure of the microparticles is affected bystimulus which weakens or breaks the interactions between themicroparticles and the substrate so as to release or detach themicroparticles from the substrate. A stimulus does not affect eachmicroparticle in a population of microparticles evenly giving rise to aprogressive erosion, destruction and/or release of the microparticles.

As used herein, the term “progressive erosion” or “progressivedestruction” or “progressive release” refers to the progressivedisintegration of the microparticles causing gradual release of anactive ingredient dispersed therein. As the microparticles disintegrate,the active ingredient is released from the microparticles.

In a specific implementation, the release of microparticles and activeingredient from the substrate is relatively continuous and constant.

Erosion may cause all or part of the microparticles to be released froma substrate or may cause detachment of all or part of the microparticlesfrom the substrate. Released or detached microparticles may fall fromthe substrate or may remain in the substrate to form, for example, ahomogeneous film.

Stimuli that cause progressive erosion, destruction or detachment of themicroparticles include, but are not limited to, physical stimuli,chemical stimuli or electrical stimuli. A physical stimulus may be suchas a mechanical contact with the treated substrate, rubbing or vibrationof the substrate, heat that may or may not be involved in mechanicalcontact. A chemical stimulus may be such as the exposure to a chemicalagent, a change in pH, a change in salt concentration, exposure tomicrobes or toxin secreted by microbes, a change in temperature and achange in humidity or the like.

In another specific, but non-limiting implementation of the presentinvention, the intensity of the stimulus determines the degree ofrelease of the active ingredient and the period over which the activeingredient is released. For example, the normal body heat of a personmay be sufficient to cause the destruction of the microparticles andrelease of the active ingredient. In a non-limiting example, thechemical stimulus may be a component of human sweat that causes theprogressive erosion of the microparticles and the release of the activeingredient. Body heat produced by physical exertion through exercise(which may also be accompanied by increased sweat production) mayincrease the degree at which the active ingredient is released.

Without intent to be limiting, many factors may be involved in releasingmicroparticles and active ingredient from a substrate. In a situationwhere, for example, a treated substrate is placed in contact with theskin, the temperature and the pH of the skin may cause or influence therelease or disintegration of the microparticles. The temperature of theskin may cause the microparticles to melt. Acidity or alkalinity of theskin may affect the components of the microparticles so as to causetheir disintegration. Normal skin surface pH is between 4 and 6.5 inhealthy people, though it varies among the different areas of the skin.Skin surface pH below 4 or above 6.5 may affect the integrity of themicroparticles. The skin also secretes chemical substances that mayaffect the integrity of the microparticles.

The microparticles may be in contact with the areas of the skin which issubjected to frequent movement such at articulations and/or joints(e.g., at elbows, ankles, knees or the neck). Skin movement at theseareas may be more frequent than at other areas of the body where thereare no articulations and/or joints. Movement of the skin createsfriction which may be accompanied by an increase in local temperature ofthe skin thus affecting the integrity of the microparticles.

In a further implementation, the active ingredient is released from thesubstrate in response to a predetermined stimulus. In this specificimplementation, the stimulus is functionally related with the activeingredient to be released. For example, a coagulant may be released froma substrate when the substrate is placed in contact with blood or acooling agent may be released from a substrate upon exposure to heat.

Progressive erosion can also result from mechanical action producingwearing of the surface of the microparticles, such as when themicroparticles are in contact with an external body or are rubbedagainst the substrate itself; can result from melting of the surface ofthe microparticles as a result of application of heat or as the resultof application of a chemical agent; can result from application ofchemical agent that degrades the substrate and/or degrades themicroparticles.

In some aspects, the release of the active ingredient is gradual, insome other aspects; the release of the active ingredient is steadyduring the entire life of the microparticle. Alternatively, the releaseof the active ingredient may be variable throughout the life of themicroparticle. Release of the active ingredient is measured per unitarea of surface of treated substrate over time.

In one aspect, progressive erosion of the microparticle and the gradualrelease of the active ingredient relate to, for example, the intensityof the stimulus applied to the microparticle and/or the substrate, thedistribution profile of the microparticles in the substrate, the natureof the formulation and the nature of the active ingredients. The factorsinfluencing the gradual release of an active ingredient from thesubstrate will be readily appreciated by those of skill in the art.

In one specific but non-limiting implementation, articles of manufacturehaving microparticles distributed therein still release microparticles,and the active ingredient dispersed therein, after 5, 10, 15, 20, 25,30, 35, 40, 45, 50, 55 or 60 wash cycles.

In a further implementation, articles of manufacture having been through5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 and 60 wash cycles stillmaintains a positive active ingredient release rate. The expression“positive active ingredient release rate” indicates that microparticlesand therefore the active ingredient dispersed therein are still beingreleased from the substrate.

In a further aspect, articles of manufacture having the microparticlesdistributed therein still retain microparticles and the activeingredient dispersed therein after 60, 55, 50, 45, 40, 35, 30, 25, 20,15, 10 or 5 wash cycles.

In a specific, but non-limiting example, the electron micrograph shownin FIG. 9B, demonstrates the microparticles obtained from a TPMAGMSformulation attached to a polyester textile after 30 wash cycles (FIG.9B). The microparticles can be distinguished when comparing FIG. 9B witha non-treated polyester textile (virgin) subjected to five wash cycles(FIG. 9A).

In a further specific implementation of the present invention, theformulations defined herein comprising an active ingredient are directlyapplied to a substrate without first obtaining microparticles, by forexample, using formulations that do not have binding agent. Suchimplementation is advantageous in situations where, for example, a fastrelease of the active ingredient from the substrate is desirable.

VIII. Release Index

In one aspect, the present invention provides for a method of improvingstabilization of one or more active ingredient in an article ofmanufacture such as a fabric, textile, fibers, foam or the like. Theformulations of microparticles as defined herein, present severaladvantages for use in this method. For example, the physical andchemical properties of the microparticles allow them to reach theinterstices, pores or cross linkage openings of a porous substrate andto be retained, trapped, attached or fixed into these interstices,pores, cavities or cross linkage openings. Because the microparticlesreach the inner core of the substrate, it gives rise to a progressiveerosion and/or disintegration of the microparticles and its gradualrelease from the substrate, thereby giving rise to gradual release ofthe active ingredient. Other factors influencing the progressive releaseof microparticles from the substrate include the nature of thesubstrate, the presence and the concentration of a binding agent as wellas the nature of the surfactant.

In a specific, but non-limiting implementation, the addition of acationic surfactant in the formulation creates an overall residualpositive charge on the surface of the microparticles. The positivelycharged microparticles adhere to, by charge neutralization, or areabsorbed by, the fibers of a textile which are generally negativelycharged. Adherence of the microparticles to the textile is alsoincreased by the addition of a binding agent into the formulation, whichbinding agent itself adheres to the fibers of the textile bridging themto the microparticles.

The advantages of treating an article of manufacture with theformulations of microparticles defined herein can be appreciated by, forexample, the resistance of the microparticles to wash cycles. As shownin FIG. 1, the percent of microparticles released from a substrate ofpolyester (referred to as P100t) and a treated substrate of nylon-cotton(in proportion of 70-30; referred to as N70C30) treated with a TPGMSformulation of microparticles or a TPMAGMS formulation ofmicroparticles. The substrate made of nylon-cotton has slightly betterretention properties than the substrate made of P100t. The datapresented in FIG. 1 also indicates that microparticles made from aTPMAGMS formulation have good adherence properties to cotton fibers.

The influence of a binding agent on the release of microparticles isalso exemplified in FIG. 2 which shows that increasing the ration ofPAC/TPMAGMS in a formulation, increases the resistance of themicroparticles to wash cycles.

An appreciation of the rate of release of microparticles from asubstrate may be obtained by, for example, calculating the releaseindex. As used herein, the “release index” refers to a constantassociated with the rate of release of microparticles from a givensurface of treated substrate over time. More particularly, the releaseindex is a representation of the decrease in mass of microparticles pera given surface of treated substrate over time. In one aspect of thepresent invention, the release index is in the range of about 1 to about20, preferably in the range of about 2 to about 7, and more preferablyin the range of about 4 to about 6.

IX. Perception Indicators

In a further non-limiting aspect, the present invention allows to createarticles of manufacture having perception indicators that arefunctionally related to the presence, the nature and/or the amount ofactive ingredient.

The perception indicators provide information regarding the presence anddistribution of the microparticles and active ingredients on thesubstrate, provide information on the type of active ingredientavailable at certain locations on the treated substrate and provideinformation regarding the amount of active ingredients remaining on, orreleased from the treated substrate.

A perception indicator may be a visual indicator, an olfactoryindicator, a tactile (or feel) or a sonic indicator.

A visual indicator may be such as a distinguishable pattern, a colorindicator, single- or multi-colored patterns, single- or multi-coloredicons and pictograms, such as an emoticon; single- or multi-coloredalphanumeric text, symbols, such and logos or the like.

In a specific aspect, the visual indicator indicates the location ofactive zones; wherein an active zone refers to a zone on the articlehaving been applied with the active ingredient (or with themicroparticles comprising it).

In a further specific, but non-limiting implementation, the presence ofdifferent active ingredients within the same substrate may be correlatedwith different perception indicators (such as a different color, motifor pattern) to inform of the location of these active ingredients andhow the substrate should be disposed of to achieve the best results.

The perception indicator also acts as wear indicator. A wear indicatorshows how much active ingredient has been released from the substrateand/or how much active ingredient remains, and indicates when thetreated substrate needs to be replenished with the active ingredient.For example, a dye may be added to the formulation of microparticles andtransferred to the substrate to indicate the location of themicroparticles. As the microparticles are released from the substratethe intensity of the dye diminishes providing the user with anappreciation of how much microparticles/active ingredient remains (orhas been released) from the substrate.

Examples of olfactory perception indicators include, but are not limitedto, a fragrance or a perfume that is applied to the substrate and whichindicates the presence of an active ingredient. Preferably, the odorindicator is proportional to the amount of active ingredient present onthe substrate and as the active ingredient diminishes, the odorindicator diminishes accordingly.

The perception indicator may also be a tactile or feel indicator whichis perceived by the skin of the user as a physical sensation. In someimplementations, application of the microparticles to the substratecreates a relief or embossments on the substrate that are felt by theskin of the user. Such relief or embossments indicate the location onthe substrate of the active ingredient. Preferably, as the activeingredient diminishes, the relief or embossments diminishes accordingly.In some particular implementations, the tactile or feel indicator mayalso micro-massage the area of the skin it is in contact with or mayexfoliate it.

In some further implementations of the present invention, the perceptionindicator indicates how much active ingredient is present at differentlocations on the substrate. Preferably, the perception indicator isadjusted so as to be proportional to the release of the activeingredient, i.e., the perception indicator diminishes proportionally tothe diminution of the active ingredient.

X. Methods for Manufacturing Perception Indicators

Perception indicators may be obtained, for example, by transferring,printing, spraying, spreading, applying, impregnating or saturating aformulation of microparticles onto a substrate so as to form aperception indicator. The indicator may be used in a number of formats,shapes, colors and textures.

In a specific, but non-limiting implementation, the perception indicatormay be applied onto the substrate to cover any where between about 0.01%to about 99% of the total surface of the substrate. Preferably, theperception indicator should be applied onto a substrate so as tomaintain the desired initial properties of the substrate such as forexample, its flexibility, its breathability, or the like.

The perception indicator may also be applied onto the substrate in arepetitive pattern. The pattern may occupy any where between about 0.01mm to about 20 cm per m² of the substrate and may repeat itself over agiven surface area of the substrate. For example, the repetitive patternhas the shape of a circle having a given diameter that is repeated avera given surface of a substrate such as for example, a textile. FIG. 13is a schematic representation of an undergarment for women (1400) ontothe inner surface of which has been applied a formulation ofmicroparticles in repetitive circles. As seen on FIG. 13, the circles(1404) are disposed on a repetitive pattern (1402) over a given surfaceof the substrate. A sufficient amount of formulation is applied to formeach circle (1404) and to create a relief on the substrate that can befelt by the skin. In this example, the microparticles that are appliedto this undergarment may comprise such active ingredients as slimmingagents. Preferably, the repetitive pattern is applied onto the substrateso as to allow the substrate to retain its properties such asflexibility and breathability.

In the following non-limiting example for the manufacture and use of avisual indicator, the material to which the microparticles are to beapplied may for example be insoles to be inserted within shoes.

To prevent and/or retard the growth of bacteria and fungi within theinsole and keep the shoe smelling fresh, a formulation of microparticleshaving a deodorizing agent as an active ingredient is applied to theinsole of a shoe through for example, the PPFV technology definedherein. An anti-bacterial agent, an anti-fungal agent and a dye-basedvisual indicator may also be included in the formulation and in themicroparticles. These agents may also be included in the applicationvehicle.

The formulation of microparticles comprising a dye-based indicator maybe applied, for example, in the pattern of a corporate logo within thearea of the insole that is normally resides under the heel of the foot.The dye-based indicator is tied to the general level of the activedeodorant agent within the insole, so that as the active ingredient isdischarged, the logo created from the dye appears to fade until theactive ingredient is exhausted and the logo completely disappears. Oncethe logo disappears, the user knows he must either replenish the activeingredient with the insole or replace the insole to avoid unpleasantfoot odor.

In the following non-limiting example for the manufacture and use of anolfactory indicator, an article of manufacture upon which theformulation of microparticles is to be applied is a shirt. In thisspecific example, the perception indicator is the fragrance itself,which is incorporated within microparticles that are activated by bodyheat to erode and release the fragrance into the surrounding air. Theformulation of microparticles containing the fragrance is applied to theshirt. As the amount of microparticles and active ingredient decreasesover time, the smell of the fragrance becomes successively less and lessnoticeable until it disappears completely when the active ingredient isexhausted.

While in this non-limiting example, both the active ingredient andolfactory indicator were identical, it is conceivable that the olfactoryindicator may be different than the active ingredient. In such a case,the olfactory indicator would be tied to the level of the activeingredient such that the level of the active ingredient could bedetermined by the intensity of the scent or fragrance. For example, theactive ingredient incorporated within the shirt may be a therapeuticalagent such as a drug. In this case, the olfactory indicator would betied to the amount of the drug within the shirt such that a wearer wouldbe able to determine the amount of drug remaining on the substrate.

In the following non-limiting example for the manufacture and use of atactile indicator, the active ingredient may be, for example, amedicinal agent or drug suitable for children. The present invention isused in the capacity of placing a predefined dosage of the activeingredient for a period of several days onto for example, the undersideof a wristband (i.e., the side that is in contact with the skin), whichthe child wears on their wrist or arm. By placing the medicinal agent incontact with the skin, the child receives their prescribed dosage of thedrug without having to actively remember to take it each day. In thisspecific example, the microparticles containing the drug may alsocomprise a foaming agent that solidifies in the presence of a particularfrequency of ultraviolet (UV) light. The formulation of microparticlesmay be applied to the underside of the wristband via a gel applicationvehicle using a solid support (such as for example, a PPFV) that appliesthe formulation to the substrate in identifiable and predictablepatterns (e.g., stripes, crosses, waves or the like). Once applied, theUV light is applied to the wristband that causes the foaming agent tosolidify into a raised pattern. Upon initial application, the raisedpattern created by the foaming agent can be identified easily. However,as the microparticles containing the active ingredient are eroded andmore and more of the drug as well as the foaming agent are dispensed thepattern on the underside of the wristband wears down.

There are various other possible perception indicators and various otherpossible applications using the invention defined herein which are allencompassed by the present specification.

XI. Methods for Replenishing a Treated Article of Manufacture

In a further implementation of the present invention, it is desirable toreplenish or reactivate a treated article of manufacture with furtheractive ingredient in situations where, for example, the activeingredient on the treated article has diminished or vanished in responseto a stimulus, or after the treated article has been through variouswash cycles, or in situations where an increase in the concentration ofactive ingredient on the treated article is required, or to add afurther active ingredient to a treated article.

Replenishing or reactivating a treated article extends the life of theactive ingredient in the treated article, thereby prolonging the releaseof the active ingredient from the article and the duration of thebeneficial properties procured by the active ingredient.

Methods for reactivation or for replenishing a substrate (or article ofmanufacture) include methods of applying a formulation of microparticlesto a substrate as defined herein. Other methods are also useful such as,but not limited to, the use of treated patches or pads which can beapplied to individual article of manufacture. In this specific, butnon-limiting example, a formulation of microparticles may be transferredfrom a treated patch or a treated pad to a selected area of the articleby contacting the treated surface of the patch or pad with the surfaceof the substrate in need of further active ingredient. The transfer maybe performed by applying pressure to the patch or the pad. The pressuremay be provided by using, for example, pressing rollers or by ironingthe patch at a temperature that will preclude premature melting of themicroparticles. A solution comprising the formulation of microparticlesmay also be sprayed onto selected areas of the article of manufacture ormay be spread.

In some implementations, the patches or pads are applied directly ontothe skin of the user. The patches may be transdermal adhesive patches todeliver a specific dose of medication through the skin and into thebloodstream; nicotine patches that releases nicotine into the body;contraceptive patches that releases contraceptive (such as syntheticestrogen and progestin hormones) to the body; dermatological patchesthat release a dermatological ingredient to the skin. Such patches maybe made in different shapes and design and may be harboring differentcolors. For example, a pad having the shape of an eye mask and beingtreated with microparticles comprising as active ingredient colostrums,such as for example bovine colostrums, may be applied onto the eyes ofthe wearer and the colostrums is delivered to the skin around the eyesof the wearer.

In a further specific, but non-limiting implementation, refillcontainers filled with formulations of microparticles defined herein areused to re-apply the active ingredient to the article. The refillcontainers may be in the from of, for example, a can, a bag, a pouch, orthe like and their content may be spread, sprayed, poured, applied,transferred, impregnated or printed onto the article. The article mayalso be soaked and/or rinsed in the formulation of microparticles or ina milieu comprising a formulation of microparticles. For example, anarticle to be replenished or reactivated with an active ingredient maybe placed in a domestic washing machine into which the content of therefill container has been placed or into which sheets of fabric softeneronto which the formulations defined herein have been applied have beenplaced.

In this specific example, the microparticles enter in contact with thearticle and are trapped on the article. Such method is useful insituations where, for example, release of the active ingredient is to beachieved over a very short period of time as the application of theformulations of microparticles may resist few wash cycles.

In a further example, treated articles are manufactured from a treatedsubstrate such as a treated fabric, fibers or textile. The treatedsubstrate may be transported in rolls or bales to the location where thearticles are to be manufactured. During transportation, it is possiblefor microparticles to be released by mechanical stimuli and it may beadvantageous to add such microparticles to the substrate prior toincorporation of the substrate into the article. Therefore, theinvention defined here allows the end user of the present invention toincorporate formulation of microparticles having the desired activeingredient at the time the substrate is converted into an article.

For example, the article to be replenished with an active ingredient maybe a shirt that contains microparticles embedded in the region of theunderarms. The formulation of microparticles applied via a solid support(such as, for example, PPFV) contains a deodorant, a fragrance and acolor indicator that are released with normal body heat to providedeodorizing properties to the wearer. The color indicator alsodisappears over time as the microparticles are eroded and the activeingredients within the shirt are exhausted. The shirt may be sold withpress-on patches that are used to replenish the active ingredients, oncethe visual indicator shows that these agents are exhausted. Since asingle patch is used to replenish the active ingredient in one region ofthe shirt, patches may typically be sold in even-numbered quantities,such as 2, 4 or 8 patches. It should be appreciated that patches mayalso be purchased independently of the shirt and may apply differentfragrances upon application. Each patch used to replenish the activeingredients in a shirt may have a color top side that differs with thefragrance applied, as well as a different color underside that containsthe microparticles having the deodorant and fragrance. The difference inthe appearance of the sides of the patch ensures that a wearer does notapply the wrong side of the patch during the replenishment procedureoutlined below. The underside of the patch may also be embossed so as toleave a visual pattern on the shirt.

To replenish the active ingredient, the shirt is turned inside out andthe patch is aligned with the area in the underarm region, with the top(colored) side facing up. Pressure is applied to the top (colored) sideof the patch for a duration sufficient to transfer the microparticlesfrom the substrate on the underside of the patch to the material in theshirt. This procedure also causes the visual indicator, corresponding tothe embossed surface of the patch, to reappear on the shirt, indicatingthat the active ingredients have been replenished.

XII. Examples of Practical Applications

The following examples demonstrate specific utilities and usefulness ofthe invention in several non-limiting scenarios and are intended toprovide the reader with an indication of how the invention definedherein may be applied in several industries, including the following:

Cosmetotextile: The invention defined herein is also useful in the fieldof cosmetotextile. The field of cosmetotextile relates to articles ofmanufacture made of textile and which comprise a substance or aformulation to be released from the textile onto one or more parts ofthe human body, wherein the substance or formulation serves anesthetical purpose. In the cosmetotextile field, the invention definedherein may be used to produce for example, upper-body-clothing articlesthat contain samples of for example, but not limited to, perfume orcologne, anti-aging creams, new depilatory lotion, anti-cellulitetreatment, slimming treatment.

Clothing: Manufacturers of clothing articles (shirts, pants, socks, orthe like) or fashion accessories (belts, hats, or the like) may use theinvention to deliver agents for cosmetic or therapeutic purposes, suchas athletic socks that contain a deodorant that is released during andafter exercise, pants that contain an anti-cellulite treatment or nightmasks with anti-wrinkle agents.

Therapeutic: pharmaceutical companies, biotechnology companies and othermay use the present invention to deliver topically or transdermally oneor more therapeutic agents to a subject.

Luggage: Producers of luggage (such as suitcases, briefcases, etc.) mayuse the invention to deliver agents for cosmetic purposes, such assuitcase interiors.

Personal Care products: Producers of personal care products (such ascreams or soaps) may use the invention to deliver agents for cosmetic ortherapeutic purposes, such as a bath towel that contains moisturizingand firming agents, furniture cleaning spray that also containsUV-blocking products and to maintain and extend the vibrancy of colorsused for fabrics that are continually exposed to the sun, such as lawnfurniture pillows and cushions, textiles or fabrics that contain insectrepellents.

Toys: Manufacturers of toys designed for use by humans may use theinvention to deliver agents for pharmaceutical or hygienic purposes,such as a baby pacifier that delivers pre-determined doses of medicine.The invention may also be applied to toys designed for animals.

Furniture and Housing Products: Producers of furniture may use theinvention to deliver agents for cosmetic or for conservation purposessuch as sprays, creams and foaming gels that maintain the cleanlinessand deodorization of the fabrics.

Carpets and Rugs: Manufacturers of carpets and rugs may use theinvention to deliver agents for cosmetic purposes, such as sprays orcreams that apply pedicure treatment to the users. The invention definedherein may also be used to deliver anti-histaminic agents.

Kitchen accessories: Producers of kitchen accessories may use theinvention to deliver agents for cosmetic or hygienic and cleansingpurposes, such as paper towels that release fragrance, soap and/ordetergents while absorbing waste liquids.

Agro-textiles: Manufacturers of textiles for agricultural uses (referredto as agro-textiles) may use the invention for prevention or industrialpurposes, such as for bags of animal feed that would contain pesticideson the exterior of the bag to kill pests while containing a hygroscopicsubstance on the interior of the bag that would absorb humidity and keepthe feed materials dry.

Geo-textiles: Producers of textiles for use in building and construction(referred to as geo textiles) may use the invention for added valuepurposes such as, for example, producing screens with fog preventingagents.

Sports, Leisure and Outdoor products: Producers of sport, leisure andoutdoor products may use the invention for cosmetic or therapeuticpurposes, such as to produce camping equipment with built-in insectrepellent.

Transportation: Manufacturers of vehicles may use the invention forcosmetic purposes, such as to integrate deodorant or therapeuticfragrances into the fabric used in seats for mass transit vehicles, liketrains, planes and automobiles.

In a more specific, but non-limiting example of practical application,the present invention relates to the manufacture of a treated glove, theinner side of which (i.e., the side of the glove in contact with theskin of the hand of the wearer) is treated with the microparticlesdefined herein. In this implementation, the treated glove is made of acotton blend. The active ingredient is a dermatological agent thatreduces skin irritation such as a corticosteroid and a moisturizer toimprove the skin's overall hydration. The microparticles having theactive ingredients dispersed therein are prepared using a formulationsuch as defined herein. Namely, the elements of the formulationincluding the dermatological agent and the moisturizer are mixedtogether. The mixed formulation is emulsified to created microparticles.A solid support is used to transfer the formulation comprising themicroparticles onto the interior surface of the gloves. The solidsupport consists of a mould of a hand that would fit inside the gloveand that is created from a PPFV fiber with dispersion mechanism locatedat the end of each finger where the fingertip would normally be located.This mechanism disperses a predefined amount of the formulation at theend of each glove finger. The glove is then removed from the mould andinserted between two moving rollers spaced appropriately to compress theglove and to spread the formulation on the inner surface of he glove. Byinserting the finger-end of the glove between the rollers first, therollers both remove forces the formulation that was deposited by themechanism at the fingertip upwards towards the open end of the glove.This step ensures that the formulation is distributed throughout theglove's interior surface while also increasing the amount ofmicroparticles that are impregnated into the cotton fibers of the glove.

In a variant of this implementation, the blended cotton spandex textileis first treated with the formulation comprising the microparticles. Theformulation is applied onto the textile by using pressing rollers. Thetreated textile is cut and sewed in a glove shape with the treatedsurface of the textile corresponding to the inner surface of the glove(i.e., the surface in contact with the skin of the wearer).

Such treated gloves can be used as inner gloves. For example, thetreated gloves may be placed in work gloves and safety gloves (e.g.,barbed wire handlers gloves, chainsaw gloves, fireman's gauntlets,welder's gloves, aircrew gloves: fire resistant, sandblasting gloves,gardening gloves, impact gloves, rubber gloves, sport and recreationalgloves). Such treated gloves can also be placed in medical gloves suchas those used by health care professionals (e.g., latex gloves orsurgical gloves). As used herein, the term “gloves” includes mittens andother variants of garments that cover the hand of a wearer.

A person skilled in the art will appreciate that variations of thisimplementation may be introduced without departing from the resultingtreated gloves.

In a more specific, but non-limiting example of practical application,the present invention relates to the manufacture of a treated bandagefor use in the preparation of orthopedic casts, such as plasterbandages. Typically, plaster bandages consist of a cotton bandage thathas been impregnated with plaster of paris, which hardens after it hasbeen made wet. In this application, the first layer of cotton bandagewhich comes in contact with the skin of the patient, is treated with aformulation of microparticles comprising a therapeutic agent such as anantibiotic to prevent and/or treat any lesions on the skin that is to becovered by the cast as well as a moisturizer or a calming lotion.

As defined above, the formulation is prepared my mixing the elementsincluding the active ingredients and microparticles are obtained byemulsifying the mixed formulation. The cotton bandage is impregnatedwith the microparticles by either soaking the bandage into theformulation comprising microparticles or by applying the formulationonto the bandages using for example, pressing rollers. The treatedbandages are dried and then applied directly onto the skin of thepatient. Subsequent layers of the bandages that have been impregnatedwith plaster of paris are applied onto the treated bandage to create thecast. As will be readily appreciated by a person skilled in the relevantart, the present invention may also be used in the preparation of manyother types of prosthesis.

In another specific example of practical application, the presentinvention relates to the manufacture of bed sheets that are impregnatedwith a formulation comprising microparticles having an activetherapeutical agent dispersed therein. In this application, theapplication vehicle may be a liquid, a gel or an aerosol spraycomprising the microparticles, for example, the sheets may be washed ina liquid comprising the microparticles or the sheets may be sprayed withan aerosol application vehicle containing the microparticles. Theapplication vehicles and treatment methods for applying themicroparticles listed above constitute a non-exhaustive list as otherpossibilities remain and would be covered by the present invention.

While the patient rests or sleeps upon the bed sheet, their body'snatural heat and movement erodes the microparticles and releases thetherapeutical agent into any exposed areas of the skin in contact withthe sheets, such as the arms, legs, back and torso area among others.

In a non-limiting scenario, this application could be used to provideregular doses of therapeutical agents.

The invention defined herein may be used to, for example, reduce andremove persistent odors from animal-related furniture, such as dog beds.In this case, the active ingredient may be a deodorizing agent speciallyformulated to counteract the general smell of the animal. In thisapplication, the application vehicle may be a paste that is initiallyspread over the fabric during the manufacture of the furniture. Thispaste comprises the microparticles and is applied by the manufacturerbefore shipping. An aerosol spray containing a formulation ofmicroparticles having the same active ingredients may also be providedseparately so that the odor-removing functionality of the furniture canbe recharged when indicated by a wear indicator. The substrate may beany fabric made of artificial fibers (such as for example, nylon) thatis used for the exterior covering of furniture. A solid support is usedto apply the paste acting as the application vehicle. In this example,the rollers may be covered with an area of PPFV to which the applicationvehicle (paste) is applied. The application vehicle (paste) is thenpressed onto the fabric, at which point the process is repeated untilall of the exposed fabric has been treated. A visible wear indicator maybe identified on an area on the fabric, such as a small patch ofspecially treated fabric that changes color as the active ingredientsare gradually exhausted. When the wear indicator shows the activeingredients are exhausted, an aerosol spray may be used to reapply theactive ingredients and maintain the odor-neutralizing ability of thetreated fabric.

In another non-limiting example, the invention defined herein may beused to apply a skin moisturizer through the application of a bath towelor cloths to a subject's body. In this case, the active ingredient is amoisturizer that rehydrates and protects skin. Further to this case, theapplication vehicle may be a liquid vehicle that contains themicroparticles with the skin moisturizer. In this example, the bathtowel is soaked in the liquid vehicle and dried before it is shipped.The microparticles within the application vehicle are electrostaticallyattracted to the material of the bath towel (which may be cotton, rayon,or polyester among others) and attach themselves to the fibers. If thebath towel is equipped with a wear indicator, the application of themicroparticles via the liquid application vehicle causes the indicatorto show that the towel has a full charge of skin moisturizer. Thesubject rubs the towel against their body to dry themselves off. Therubbing motion of the towel against the skin causes the microparticlesto erode and the skin moisturizer to be released. Over time, the amountof moisturizer released onto the skin decreases as microparticles in thebath towel are exhausted. Once the microparticles are exhausted, thesubjects may replenish the towel by re-soaking it into the liquidapplication vehicle.

In a further non-limiting example of the present invention, theformulation comprising a color dye and an active ingredient (such as forexample, taurine) is prepared as defined herein. The formulation isapplied to a sticker-type non-permanent tattoo support in a desiredshape or design and then dried. The treated sticker-type tattoo supportis applied onto the skin and the formulation (as well as the shape ordesign) is transferred onto the skin by rubbing the treated sticker-typetattoo support with a damp washcloth. In this specific example, taurineis absorbed transdermally by the skin during the wear period of thetattoo.

According to a further aspect, the present invention relates toformulations of microparticles, application vehicles comprisingmicroparticles and/or treated supports, as defined herein that areprovided in kits or commercial packages. Such kits or commercialpackages typically comprise instructions indicating for example, how touse the formulations, application vehicles and treated supports, thenature of the active ingredient(s) (if any provided), the recommendeduses, the recommended period of time over which the use should becarried out, the expiry date, etc.

It should be understood that the industries and commercial applicationsidentified above constitute a non-exhaustive list and that othercommercial applications remain and are intended to be covered by thisinvention and this application.

The following examples are to illustrate different implementations ofthe invention defined herein with no intention of restricting theinvention to these examples.

XIII. Experiments and Data Analysis Example 1 Preparation of aFormulation Comprising Microparticles

The following example illustrates the manner of preparation of 20 g of aformulation comprising 10% of microparticles in water, wherein themicroparticles comprise 5% Ceramide A as active ingredient, and abinding agent is used to achieve a microparticles:binding agent ratio of0.5:1. Table 3 indicates the elements and the amounts thereof enteringthe formulation.

TABLE 3 Formulation Amount in Elements grams (g) PART A Tripalmitin(100%, TP) [A1] 1.24 Glycerol monosterate (GMS) 0.38 (100%) [A2]Paraffin (PARA) (100%) [A3] 0.28 Ceramide-A (CER) (100%) [A4] 0.10 PARTB Cetyl trimethylammonium chloride 0.19 (CTAC) (53%) Water (100%) 15.59PART C TriPoly AC M4445 (PAC) (45%) 2.22 Total 20.00

Preparation of a Hydrophobic Mixture:

PART A was prepared in an aluminum crucible, the mass of which waspreviously determined [A0] using an analytical balance. The crucible wasweighted after addition of each of the elements of PART A: namely, [A1],[A2], [A3] and [A4]. The crucible was then heated in order to melt theelements. The melted elements were stirred with a spatula. The aluminumcrucible was then removed from the heat source and was cooled down untilthe mixture had solidified, at which stage the mass of the aluminumcrucible was measured [Atot].

Preparation of PART B:

Part B was prepared into a 50 ml beaker (PYREX™). The empty beaker wasweighted prior to addition of the elements [B0] and after addition ofeach of CTAC [CATC] and water [WATER]. The beaker containing CTAC andwater was then heated to between about 60° C. and about 70° C. At thispoint, the aluminum crucible was heated again so as to melt completelythe PART A mixture. Melted PART A was added into PART B and mixed toobtain a coarse emulsion. The mass of the beaker was weighted again[Btot]. The mass of the aluminum crucible was measured [Afin].

Formation of Microparticles by Homogenization:

The coarse emulsion containing PART A and PART B was homogenized oneminute using a Silverson™ homogenizer at maximum speed (at around 10 000rpm). The beaker was cooled down in a water bath at temperatures equalto or inferior of 15° C. and the homogenization was resumed for oneminute at minimum speed. The beaker containing the formulation ofmicroparticles was then removed from the water bath.

Addition of a Binding Agent:

The mass of the beaker containing the formulation of microparticles wasdetermined [Bfin]. PART C was then added and mixed manually with thebeaker containing PART A and PART B. The mass of the beaker was noted[C].

The formulation of microparticles obtained by this procedure may beapplied to a substrate or may be kept into a hermetic container forlater use.

Example 2 Transfer of the Formulation of Microparticles onto a SolidSupport

A solid support was prepared using polypropylene (Gemex PPC3119™) (seeFIG. 10A, (1002)) and glass fiber (Fiba Tape™) (see FIG. 10A, (1004))which were assembled together by pressing the two material against eachother using pressing rollers (Richeson™ 11″ Baby Press) (see forexample, FIG. 10A).

The solid support was weighted [S0]. The formulation was applied ontothe solid support so as to fill up the recesses defined by the glassfiber net applied onto the polypropylene film. The solid support withthe applied formulation was weighted [S1]. The mass of the formulationwas determined by calculating the difference ([S1]−[S0]). Theformulation was dried until the mass of the formulation in the recesseshad diminished by half [S2].

Example 3 Transferring the Formulation of Microparticles from a SolidSupport to a Substrate

As shown in FIG. 11, the surface of the textile (substrate) onto whichthe formulation is to be transferred, should preferably be larger thanthe surface of the solid support. In this example, pressing rollers(Richeson 11″ Baby Press) (1100) are used to transfer the microparticlesfrom the solid support (1104), having a mesh of for example glass fiber(1106), onto a textile (1108).

A foam (1102), preferably having a larger surface than the textile(1108) is applied to the plate onto which the textile is placed (i.e.,so as to be in contact with the surface of the substrate that will notbe applied with the formulation) to facilitate contact between theformulation on the support (1104) and the textile (1108).

The textile (1108) is weighted [E0] and placed onto the foam (1102). Thesurface of the textile that will be applied with the formulation shouldbe facing up. The support (1104) having the formulation ofmicroparticles applied thereon is placed onto the textile (1108) so asto place the microparticles in contact with the textile (1108).Optionally, a further foam may be applied between the roller (1100) andthe support (1104) (not shown). The press is operated so as to press thesandwich “foam-textile-support” or “foam-textile-support-foam” on itsentire length. The foam and the substrate are removed and the treatedtextile is weighted. The support devoid of formulation is weighted[Sfin]. The treated textile is dried at room temperature with or withoutapplication of extra ventilation, such as by using a table fan. Oncedried, the textile is weighted [Efin].

FIG. 5 indicates the percent of formulation transferred from a solidsupport to a rigid-surfaced substrate or to a flexible-surfacedsubstrate (use of foam). Notably, the percent of formulation transferredis increased when foam is used, indicating that the efficiency oftransfer is improved when the substrate is at least partially flexible.

Example 4 Data Analysis

The concentration of microparticles and elements entering in thepreparation thereof may be determined using the measurements obtained inthe preparation of the formulation comprising the microparticles:

TABLE 4 Determining the concentration of microparticles Elements Amount(%) TP [A1] 100*(A1 − A0)/(A4 − A0) GMS [A2] 100*(A2 − A1)/(A4 − A0)PARA [A3] 100*(A3 − A2)/(A4 − A0) CER [A4] 100*(A4 − A3)/(A4 − A0)

The concentration of microparticles and surfactant in the beaker beforeaddition of the binding agent (initial or “,”) may be calculated asfollows:

Microparticle (referred to as μPi)=(A4−Afin)/(Btot−B ₀)

CTACi=(CTAC−B0)*0.53/(Btot−B0)

The following formula may be used to determine the concentration ofmicroparticles (μPi), surfactant (CTAC) and binding agent (PAC) in theformulation:

TABLE 5 Determining the concentration of microparticles Formula μPi %(p/p) 100*μPi*(Bfin − B0)/(C − B0) PAC, % (p/p) 100*PAC*(C −Bfin)*0.45/(C − B0) CTAC, % (p/p) 100*CTACi*(Bfin − B0)/(C − B0)

The percent efficiency of transfer of the formulation of microparticlesfrom the support to the textile may be calculated as follows:

Waste (%)=100*(Sfin−S0)/(S2−S0)

Transfer (%)=100−Waste

The fraction of each element in the dry material (microparticles, activeingredient, binding agent, and surfactant) remaining on the treatedtextile may be calculated as follows:

F _(PAC,dry)=PAC/(CTAC+PAC+μPi)

F _(CTAC,dry)=CTAC/(CTAC+PAC+μPi)

F _(μPi,dry)=□μPi/(CTAC+PAC+μPi)

The surface concentration of each element may be calculated as follows:

P _(textile) (g/m²)=F _(μPi,dry)*(Efin−E0)/surface

PAC_(textile) (g/m²)=F _(PAC,dry)*(Efin−E0)/surface

CTAC_(textile) (g/m²)=F _(CTAC,dry)*(Efin−E0)/surface

wherein the surface is expressed in square meter (m²).

Example 5 Melting of the Microparticles

The temperature at which the microparticles melt may be determined fromthe formulation remaining on the aluminum crucible (Afin-A0) or may bedetermined on the treated textile (in the dry state) using a meltingpoint apparatus such as a AT-HLM (Qinc) apparatus or using differentialscanning calorimeter or thermal analysis. Methods and apparatus todetermine melting temperatures are well known in the art.

Example 6 Testing the Resistance of a Treated Substrate to Wash Cycles

Resistance of a treated textile to wash cycles was assessed bydetermining the amount of microparticles remaining on the treatedtextile (or by determining the amount of microparticles released fromthe treated textile) after consecutive wash cycles.

Testing the resistance of a treated textile to wash cycles was performedin the following conditions:

-   -   Detergent=Zero™ (Woolite™),    -   Concentration of detergent in the washing solution=1 g of Zero™        per liter of water;    -   Temperature of the washing solution=23° C.;        -   pH of the washing solution=8.1; and    -   Temperature of the rinsing water=13° C.;

The procedure includes obtaining a sample of 7 cm×7 cm of a generallyflat textile. Generally, the sample may be obtained from a textile whichis of commercial interest and which is to enter in the fabrication of anarticle of manufacture of interest. To avoid raveling of the sampleduring the test and to prevent loss in sample mass, the edges of thesample are doubled over and sewed using a conventional sewing machine orsewed manually using a needle and a thread. The techniques to sew theedges of a textile to prevent raveling will be well known by those ofskill in the art.

If the sample contains a substantial amount of synthetic fibers such aspolyester, nylon or the like (e.g., 100% nylon (N100), 65% polyester and35% cotton (P65C35), 70% nylon and 30% cotton (N70C30), 90% nylon and10% spandex (N90S10), 100% cotton (C100), 95% cotton and 5% spandex(C95S05), (P100m) and Denim), the edges of the sample may also be weldedusing a heat source such as a blowtorch, a welding torch or other flamesources.

Only the edges of the sample should be subjected to sewing or welding sothat the remaining of the sample is suitable for deposition of aformulation of microparticles. If the edges of the sample are welded,the welded sample should be allowed to cool down before the formulationis applied thereon.

The mass of the sample is weighed, preferably on an analytical balanceto the 4^(th) decimal [TS].

The formulation of microparticles as obtained in EXAMPLE 1 was appliedto the sample using the techniques as defined in EXAMPLE 2 and EXAMPLE3. The mass of the treated sample was weighed on an analytical balanceto the 4^(th) decimal. The treated sample was then dried atapproximately 23° C. for approximately 1½ hour and/or until the mass ofthe treated sample had diminished by approximately 50%. The watercontent remaining in the sample may be determined by weighing the sampleor by any other suitable method. The mass of the treated sample wasdetermined again using an analytical balance [TSini].

Suitable containers for use in this test have a volume of 500 ml and canbe hermetically closed to avoid leakage of the washing solution duringthe procedure.

A wash cycle consists in filling the container with 250 ml of washingsolution as defined above. The washing solution was manually poured intothe container. The volume of wash solution poured into the containershould preferably be smaller then the volume of the container to allowfor movement of the wash solution in the container during the procedure.The treated sample was then placed in the container and the containerwas closed hermetically.

The container was rotated at a frequency of 1 Hz, for 15 minutes so thatat the end of the 15-minute rotation period, the container had beenthrough about 900 rotations. To rotate the container, the container wasmounted on the rotation axis of a tilt-head stand mixer (obtained fromKitchen-Aid™) having a motor wattage of 325 watts such as illustrated inFIG. 12. The stand mixer (1200) comprises a platform (1204) mounted inthe axis of the motor of the stand mixer (1200). One end of the platformis rotably mounted to the stand mixer through the attachment port (1206)of the stand mixer (1200). Optionally, the other end of platform is alsorotably mounted on a supporting plate (1210) through a supporting pin(1208) received in a recess in the supporting plate (1210). It will beunderstood that, in this specific setting, the supporting plate (1210)is required to prevent the stand mixer (1200) from tipping over due tothe weight of the platform (1204) and the container (1202) mountedthereon. The container (1202) is attached to the platform (1204) usingsuitable attachment means such as, but not limited to, elastics, tapes,latches, etc. Any other technique and/or apparatus to rotate thecontainer are also intended to be covered by the present specification.

At the end of the rotation period, the container was open andsubstantially all of the washing solution was gently removed whilepreventing the sample from exiting the container. The washing solutionwas poured into a waste container. The wash solution may be pouredmanually or by any means to transport the wash solution out of thecontainer such as by using a pipette of suitable size.

The treated sample was then rinsed twice with 250 ml of rinsing water.To rinse, 250 ml of rinsing water was poured into the container. Thecontainer was closed hermetically and rotated as described above forabout 1 minute. The container was open and substantially all of therinsing water was poured out of the container and added to the wastecontainer comprising the wash solution. Another 250 ml of rinsing waterwas added to the container. The container was hermetically closed androtated for about 1 minute. The container was open and substantially allof the rinsing water was poured out of the container and added to thewaste container having the wash solution and the first rinsing water. By“substantially all of the rinsing water” is meant that the inside of thecontainer is visibly free of liquid body.

The treated sample was wrung manually such as by using a rotating saladspinner. The treated sample was rotated in the salad spinner for about 1minute.

The treated sample was then air-dried at approximately 23° C. forapproximately 1½ hour with or without application of extra ventilationprovided by a table fan and/or until the treated sample had lost 50% ofits initial mass (i.e., 50% of [TSini]). Other methods to determine thewater content of the sample may be used. Such techniques and apparatusare well known to those of skill in the art.

To recover any fiber or any material from the sample that may have beenlost during the wash cycle, the content of the waste container (i.e.,the wash solution and the rinsing solution) may be filtered usingconventional methods used in the art, such as for example, by usingfilters of suitable pore size and a vacuum system. The pores of thefilters should be small enough to prevent fibers of the sample to passthough the pores during filtration. The fibers obtained from filtrationof the wash and rinse solutions are air-dried at approximately 23° C.for approximately 1½ hour.

The weight of the treated sample (and any material recovered fromfiltration of the waste solution) is determined to the 4^(th) decimalusing an analytical balance [TSfin_(wash 1)]. The weight ofmicroparticles remaining on the sample is determined using the formula:

[TSini]−[TSfin_(wash x)]=weight of microparticles released duringwashing x;

[TSfin_(wash x)]−[TS]=weight of microparticles remaining on the sample;

wherein “_(x)” indicates the number of wash cycles the sample has beenthrough.

The wash cycle test was repeated at least 40 times (40 wash cycles) forthe same sample. The weight of the microparticles remaining on thesample after each wash cycle was determined. The data obtained wasplotted as illustrated in FIGS. 3A to 3C. For better accuracy of theresults, the test was repeated with 3 other treated samples using thesame condition as above. An average of the mass of microparticlesremaining on the samples was obtained from the four samples tested andplotted against the number of wash cycles. Not more than one sampleshould be placed in the same container as the samples may adhere to oneanother and the results of the test may be corrupted.

FIGS. 3A, 3B and 3C illustrate the percent microparticles remaining onthe samples following the indicated number of wash cycles. FIGS. 3A, 3Band 3C also show the influence of a binding agent on the release ofmicroparticles from the treated textile. Table 6 indicates theconditions used in this experiment.

TABLE 6 Experimental conditions Binding Ratio binding Type of Totalinitial Formulation agent agent/microparticle Transfer (g/m²) LASA — 0humid 13 and 16 LASA PAC 0.5 humid 18 and 22 LASA — 0 dry 14 LASAKAR — 0humid 11, 17 and 17 LASAKAR PAC 0.5 humid 15, 24 and 27 LASAKAR — 0 dry16 and 19 TPMAGMS — 0 humid 25 TPMAGMS PAC 0.5 humid 33 TPMAGMS — 0humid 13 TPMAGMS PAC 1.0 humid 18 TPMAGMS — 0 dry  8

As shown in FIG. 3A, after 20 wash cycles approximately 30% of themicroparticles obtained from a LASA formulation remained on the textilein the absence of binding agent (PAC=0, ini=14, dry transfer). Additionof a binding agent to the LASA formulation in a ratio of bindingagent/microparticles of 0.5 (PAC/microparticles=0.5, ini=18 andPAC/microparticles=0.5, ini=22), increases the percent of microparticlesremaining on the substrate to approximately 65% after 20 wash cycles and55% after 30 wash cycles (FIG. 3A).

As shown in FIG. 3B, for microparticles obtained from a LASAKARformulation, approximately 25% of microparticles remains on the textileafter 20 wash cycles in the absence of binding agent (PAC=0, ini=19, drytransfer and PAC=0, ini=16, Perfumed, dry transfer), this valueincreases to approximately 45% after 40 wash cycles in the presence of abinding agent, wherein the ratio of binding agent/microparticles is 0.5(PAC/microparticles=0.5, ini=24 and PAC/microparticles=0.5, ini=27).

FIG. 3C shows that approximately 45% of microparticles obtained from aTPMAGMS formulation remains after 20 wash cycles in the absence of abinding agent (PAC=0, ini=8, dry transfer). Addition of a binding agentin a ratio of binding agent/microparticles is of 1.0(PAC/microparticles=1.0, ini=18), increases the percent ofmicroparticles remaining on the textile to approximately 85% after 20wash cycles.

The test allows determining the rate of release of the microparticlesfrom the sample. The data obtained from the test demonstrates that therate of release of microparticles from the sample is positive andconstant at least between 10 and 20 wash cycles and/or constant at leastbetween 20 and 30 wash cycles. A positive rate of release indicates thatmicroparticles and therefore active ingredient dispersed therein arestill being released from the sample at least between 10 and 20 washcycles and/or at least between 20 and 30 wash cycles.

The data also demonstrates that the amount of microparticles releasedfrom the sample between 15 and 20 wash cycles is about 2 to about 3times the amount of microparticles released from the substrate between30 to 40 wash cycles.

Example 7 Determining the Release Index

The release index is a correlation of the rate of release ofmicroparticles over a determined surface of treated substrate over time(evaluated in terms of number of wash cycles). The rate of release ofmicroparticles obtained from LASA, LASAKAR and TPMAGMS formulations wereobtained from the data presented in FIGS. 3A, 3B and 3C. FIG. 4A showsthe rate analysis of microparticles obtained from a LASA formulation,FIG. 4B shows the rate analysis of microparticles obtained from aLASAKAR formulation and FIG. 4C shows the rate analysis ofmicroparticles obtained from a TPMAGMS formulation.

Table 7 provides the rate constant and the release index ofmicroparticles obtained from the indicated formulation:

TABLE 7 Release Index First Order Rate Release Index FormulationConstant (RI) LASA −0.067 7 LASA-PAC −0.019 2 LASA-MOLTEN −0.059 6LASAKAR −0.173 17 LASAKAR-PAC −0.026 3 LASAKAR-MOLTEN −0.085 8 TPMAGMS−0.189 19 TPMAGMS-PAC −0.009 1 TPMAGMS-MOLTEN −0.036 4

The release Index is calculated as follow:

Release Index (RI)=Round(−100*rate constant)

The release index indicated in Table 7 corresponds to the kinetic of therelease of microparticles in a soapy solution.

The half-life of the microparticles on a substrate such as a textilecorresponds to the number of wash cycles required to remove half of theinitial amount of microparticles applied to the substrate and iscalculated using the following formula:

T_(1/2)=69/RI

The data presented in FIGS. 4A to 4C and in Table 7, indicates that therate at which the microparticles are released (release index) from asubstrate is gradual and constant.

Example 8 Transfer of Microparticles from a Substrate onto the Skin

Tests have been performed to assess the efficiency of microparticlestransfer from a substrate to human skin as well as to determine theinfluence of the temperature on the transfer efficiency.

Samples (or patches) of polyester treated with LASA or LASAKARformulated microparticles with or without a binding agent (PAC; in aratio of binding agent/microparticles of approximately 0.5) were appliedonto the skin for a period of 30 min. The treated polyester samples wereplaced on three zones of the skin having the following temperatures 31°C., 33° C. and 34° C. and not covering an articulation and/or a joint.The samples were applied on a surface of 25 cm² in an amount ofapproximately 8 g/m² for all the formulations tested except for theLASA/PAC formulation, which was applied at 16 g/m². The amount offormulation transferred is indicated in FIG. 6.

FIG. 6 shows, inter alia, that the amount of LASA formulatedmicroparticles transferred increases significantly with an increase intemperature. However, the amount LASAKAR formulated microparticlestransferred was similar at all the temperatures tested. This observationmay be explained by the fact that this formulation comprises shea butterwhich partly melts at room temperature. In this experiment, the presenceof a binding agent did not significantly influence the transfer.

Example 9 Formulations of Microparticles Comprising Natural Butters

Other formulations were prepared using the elements indicated in Table8:

TABLE 8 Formulation comprising natural butters % final Weight (g)Distilled H₂O 84.1 107.2067 Surfactant CTAC 0.3 g/g 0.7 3.0333 [CTAC-30(30%), Ammonyx, Stepan, Northfield, U.S.] Anti-oxydant Vitamine E 0.20.2600 [Oil 28 000 IU (acetate tocopheryl), Life, Toronto, Canada]Emulsifier GMS 1.05 1.3650 [Cutina, Catalog No. CG83470001, CognisOleochemicals Canada Ltd, Mississauga, Canada] Formulation comprisingmicroparticles Fatty acids Stearic acid (SA) 5.85 7.6050 [Emersol 132,Cat No. N18KXXX124, Cognis Oleochemicals Canada Ltd, Mississauga, CanadaContent: 45.5% stearic acid, 50% palmitic acid, 2.5% myristic acid, 1.5%heptadecanoic acid] Palmitic acid (PA) 3.15 4.0950 [97%, Catalog No.2712G2-698PNLK0034, Croda, Vaughan, Canada (Palm-Oleo SDN) BHD] Activeingredients Olive butter (O) 1.98 2.5740 [Catalog No. 2176 NewDimensions Aromatics Inc., Brampton, Canada] Mango butter (M) 1.982.5740 [Catalog No. 3311 New Dimensions Aromatics Inc., Brampton,Canada] Grape seed butter (G) 0.495 0.6435 [Catalog No. 2174 NewDimensions Aromatics Inc., Brampton, Canada] Shea butter (KAR)) 0.3960.5148 [Catalog No. 16009-A13 New Dimensions Aromatics Inc., Brampton,Canada] Lemon butter (L) 0.099 0.1287 [Catalog No. 216F07-01 NewDimensions Aromatics Inc., Brampton, Canada] Total 100 130

In this particular example, the stearic acid used was composed of 45.5%stearic acid, 50% palmitic acid, 2.5% myristic acid and 1.5%heptadecanoic acid, therefore the final % of stearic acid in theformulation was 2.66%, the final % of palmitic acid in the formulationwas 5.3505% [(5.85%×50%)+(3.15%×97% contained in palmitic acid)], thefinal % of myristic acid in the formulation was 0.146% and the final %of heptadecanoic acid in the formulation was 0.088%.

Combining the Elements—First Procedure:

The fatty acids, butters, GMS and vitamin E were weighted and combinedinto a first 100 ml beaker (beaker no. 1) (PYREX™). Beaker no. 1 wascovered with aluminum foil and placed into a 77° C. incubator until allthe elements had melted.

Distilled water and CTAC were combined in a second 200 ml beaker (beakerno. 2) (PYREX™) having a diameter of 5 cm. Beaker no. 2 was covered withaluminum foil and placed in a 77° C. water bath for approximately 15minutes until the content of beaker no. 1 was completely melted.

Once the content of beaker no. 1 was melted and the content of beakerno. 2 had reached a temperature of 77° C., the content of beaker no. 1was poured into beaker no. 2.

Combining the Elements—Second Procedure (Alternative to the FirstProcedure):

All the elements except for CTAC were weighed into a 200 ml beakerhaving a diameter of 5 cm. The beaker was covered with an aluminum foiland placed into a 77° C. water bath. CTAC was weighed and added to thebeaker right before homogenization.

The second procedure presents certain advantages over the firstprocedure, namely, the melting time of the fatty acids and butters isdecreased compared to the first procedure and waste of elements isminimized as the second procedure does not require transfer from beakerto beaker. The formulation does not appear to be affected by which ofthe first or second procedure is carried out.

Homogenization:

A Sylverson™ L4R homogenizer (Sylverson L4R, Sylverson Machines Ltd.,Chesham, UK) equipped with a square hole high sheer screen work head wasused for homogenization. While carrying the first (or the secondprocedure), the homogenizer was pre-heated by immersing the mixing headof the homogenizer into boiled distilled water. The mixing head was thenactivated to liberate air bubbles that may have been trapped into thesystem.

For homogenization, the beaker having the formulation was placed into awater bath so as to maintain the formulation at a temperature of about68° C. during the homogenization step. The homogenizer was set at aspeed of 11 500 rpm and the formulation was homogenized for betweenabout 4 to about 6 minutes (the formulation could be homogenized forabout 2 to about 16 minutes). Speed of around 7 300 rpm could also beused to obtain formulations having the desired thickness.

Microscopy:

The size of the microparticles was monitored during and afterhomogenization using a microscope Olympus CX-30. Microparticles having acircular shape, a smooth texture, showing a homogeneous dispersionthroughout the formulation and having a size of between about 2 to about20 microns were observed. It was also observed that the faster the speedat which a formulation is homogenized, the smaller the size of themicroparticles obtained.

Cooling:

Following homogenization, the formulation was cooled at room temperature(approximately 21° C.) with occasional manual stirring. The rate ofcooling was measured to be approximately 1° C./min.

Other cooling procedures may also be used. Namely, the formulation canbe cooled in a water bath having a temperature of approximately 15° C.The formulation may be cooled using a copper coil in which water(approximately 20° C.) circulates. A rate of cooling of about 1.5°C./min can be achieved with the latter procedure.

Thickness:

Thickness of the formulation was established according to known orrecognized visual parameters, namely a formulation showing a thicknessthat is similar to a lotion was attributed the value “0”, a formulationshowing a thickness similar to mustard was attributed a value of “1”, aformulation showing a thickness similar to butter (at room temperature)was attributed the value “2”, a formulation showing a thickness similarto whipped butter was attributed a value of “3”, a formulation showing athickness similar firm cream was attributed with a value of “4” and aformulation showing a thickness similar to lard was attributed with avalue of “5”. The formulation obtained with the elements as indicated inTable 8 showed a thickness of 4.

Example 10 Other Formulations

Other formulations having the composition indicated in Table 10 belowwere prepared and were tested for the indicated parameters. In Table 10,“SA” refers to stearic acid, “PA” refers to palmitic acid, “LA” refersto lauric acid, “0” refers to olive butter, “M” refers to mango butter,“G” refers to grape seed butter, “KAR” refers to shea butter, “L” refersto lemon butter and “GMS” refers to glycerol monostearate.

TABLE 8 Formulations Time Rate Temp Temp Temp hom cooling Thick- Ini homSize fusion GMS Temp Formulation rpm min ° C./min ness ° C. ° C. μm ° C.% cooling SAPAOMGKARL- 3 6 −1.1 1 66 64 <20 45.7 7 RT GMS SAPAOMGKARL- 36 −0.62 2 65 60 <20&<40 46 7 RT GMS SAPAOMGKARL- 3 6 −0.59 2 — — 20 < 4045.4 8 RT GMS SAPAOMGKARL- 6 6 −1.2 3 69 68  5 < 20 — 7 RT GMSSAPAOMGKARL- 7 6 −0.7 3 69 69  5 < 15 — 7 RT GMS SAPAOMGKARL- 7 6 −2.4 369 69  7 < 15 — 7 RT GMS SAPAOMGKARL- 7 6 −0.8 4 68 68  5 < 20 — 7 RTGMS SAPAOMGKARL- 7 6 −0.95 4 68 64-68    5 < 15 — 7 RT GMS SAPAOMGKARL-7 2 −0.97 4 69 65-69    5 < 15 — 7 RT GMS SAPAOMGKARL- 7 4 −1.36 1-3 6665-66    5 < 15 — 7 RT GMS SAPAOMGKARL- 7 6 −1.36 2-3 66 60-67    5 < 20— 7 RT GMS SAPAOMGKARL- 7 6 −0.72 1-2 67 70-71    5 < 15 — 5 RT GMSSAPAOMGKARL- 7 6 −1.08 3 70 70  4 < 20 — 7 RT GMS SAPAOMGKARL- 7 4 −1.33.5 71 70  4 < 20 — 7 RT GMS SAPALAOMGKARL- 7 6 −1.07 4 70 70-68.5  4 <20 — 7 RT GMS SAPALAOMGKARL- 4 4 −1.4 3 72 72-73.5  4 < 20 — 7 RT GMSSAPAOMGKARL- 7 4 −0.95 — —  4 < 15 — 7 RT GMS SAPA-GMS 7 4 −0.77 1.5 6866-68    4 < 15 — 7 RT SAPAOMGKARLV- 7 4 — 4 — —  1 < 15 — 7 RT GMS rpm= rotation per minute Time hom min = homogenization time in minute RateCooling ° C./min = rate of cooling of the formulation in Celsius perminute Thickness = thickness of the formulation Temp Ini ° C. = initialtemperature of the formulation in Celsius Temp homo ° C. = temperaturein Celsius of the formulation when homogenization is carried out Size μm= size of the microparticles in μm Temp fusion ° C. = fusion temperatureGMS % = percent GMS present in the formulation Temp cooling ° C. =cooling temperature RT = room temperature, approximately 21° C. — = notdetermined

The thickness of the formulations is as defined in Example 8.

While the invention has been described in connection with specificembodiments thereof, it will be understood that it is capable of furthermodifications and this application is intended to cover any variations,uses, or adaptations of the invention following, in general, theprinciples of the invention and including such departures from thepresent disclosure as come within known or customary practice within theart to which the invention pertains and as may be applied to theessential features hereinbefore set forth, and as follows in the scopeof the appended claims.

All published documents mentioned in the above specification are hereinincorporated by reference.

1.-79. (canceled)
 80. A formulation for obtaining microparticles,comprising a carrier material, wherein the carrier material includes oneor more of: a lipid, a fatty acid-based lipid, a fatty acid or aglyceride or any combination thereof.
 81. A formulation as defined inclaim 80, wherein the carrier material is caproic acid, caprylic acid,capric acid, undecanoic acid, lauric acid, tridecanoic acid, myristicacid, pentadecanoic acid, palmitic acid, heptadecanoic acid, stearicacid, oleic acid, elaidic acid, linoleic acid, linolenic acid, arachidicacid, arachidonic acid, a fatty acid derivative, tripalmitin, tristearinor glycerol monostearate or any combination thereof.
 82. A formulationas defined in claim 80 or 81, further comprising an active ingredient.83.-85. (canceled)
 86. A formulation as defined in claim 80, wherein theformulation comprises a plurality of microparticles.
 87. A formulationas defined in claim 82, wherein the active ingredient is a cosmeticagent, a therapeutic agent, a pharmaceutical agent, a nutraceuticalagent, a cleansing agent, a detoxifying agent or a fragrance or anycombination thereof.
 88. A formulation as defined in claim 80, whereinthe carrier material includes a natural butter.
 89. A formulation asdefined in claim 88, wherein the natural butter is olive butter, mangobutter, grape seed butter, shea butter or lemon butter or anycombination thereof.
 90. A formulation as defined in claim 80, whereinthe formulation further comprises a binding agent.
 91. A formulation asdefined in claim 80, wherein the binding agent is a polyacrylic (PAC), apolyurethane (PU), a polysiloxane (POL), a polyvinylpyrrolidone (PVP), aguar gum or an acrylic base or any combination thereof.
 92. Aformulation as defined in claim 80, wherein one or more of themicroparticles have a size in the range from about 0.1 μm and about 200μm.
 93. A formulation as defined in claim 80, wherein one or more of themicroparticle have a size in the range of about 2 μm and about 20 μm.94. A formulation as defined in claim 80, wherein the microparticleshave a melting temperature between about 20° C. and about 60° C.
 95. Aformulation as defined in claim 80, further comprising a surfactant. 96.A formulation as defined in claim 80, wherein the microparticleundergoes progressive erosion in response to a stimulus to cause gradualrelease of the active ingredient.